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Mucormycosis is a life-threatening fungal disease in patients with hematological malignancies. The diagnosis of pulmonary mucormycosis is particularly challenging. We describe 3 mucormycosis cases with an uncommon presentation in patients whose cavitary lung disease was attributed to well documented bacterial infection, although evolution and reassessment established mucormycosis as the underlying disease.

For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802., Competing Interests: Potential conflicts of interest. A. F. had/has research grants from Pfizer, Merck, Janssen, CyanVac, VaxCo, Moderna, and BioFire Diagnostics; fees for advisory boards from GSK, ADMA Biologics, and Sanofi Pasteur; and fees for data safety monitoring board from Novavax. M. E. S. had/has grants from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) during the conduct of the study (5UM1AI069470); grants from NIH/NIAID and Gates Foundation outside the submitted work; and grants to her institution from Merck Sharpe and Dohme, Sanofi, and Gilead outside of the submitted work. S. R. W. has received institutional funding from the NIH/NIAID; institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; has participated on data safety monitoring or advisory boards for Janssen Vaccines/Johnson & Johnson and BioNTech; and his spouse holds stock/stock options in Regeneron Pharmaceuticals. C. M. E. has received research grants from Merck and AstraZeneca; and has participated in Sanofi, Janssen, and Gilead advisory board meetings. N. R. is a paid safety consultant for ICON, CyanVac, and EMMES; served on selected advisory boards for Sanofi, Seqirus, Pfizer, and Moderna; and receives funds to their institution to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company, and Pfizer. C. L. G. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies; and grants to her institution from Gilead and ViiV outside of the submitted work. K. L. K. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689); and from Novavax outside of the submitted work. J. A. G. is employed by and holds stock in AstraZeneca. E. A. H. received fees from Oxford University for time spent adjudicating end points for the AstraZeneca/Oxford SARS-CoV-2 vaccine trials conducted in the UK, South Africa, and Brazil. M. D. T. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions., Methods: A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods., Results: A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus., Conclusions: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials., Competing Interests: Potential conflicts of interest. O. A. received salary support from research funding paid to UCLA by Moderna, Inc. A. T. reports that this project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. C. L. G.’s institution received funding from the NIH for salary support for her role as site Principal Investigator for the Moderna Phase 3 trial and site Principle and Co-Chair for the Novavax Phase 3 trial. N. R. received research grants from Pfizer, Merck, Sanofi, Quidel, Immorna, Vaccine Company, and Lilly through her institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi and Moderna. N. R. serves on safety committees for ICON and EMMES and is a member of the Moderna, Sanofi, Seqirus, and Pfizer selected Advisory boards. I. H. is an employee of AstraZeneca and holds/may hold stock in AstraZeneca. A. R. F. reports grant support from Janssen, Pfizer, Moderna, CyanVac, VaxCo, and BioFire Diagnostics; advisory board fees from Arrowhead and GSK; travel reimbursement from GSK and Sanofi and fees for DSMB from Novavax. B. L. is an employee of Moderna, Inc. and may own stock/stock options in the company. J. S. declares support for the submitted work from the Janssen Pharmaceutical Companies of Johnson & Johnson and partial support (in the form of funding to his institution) from BARDA for the submitted work, declares support from the Janssen Pharmaceutical Companies of Johnson & Johnson and BARDA funding for part of this work, has patents on invention of the Janssen COVID-19 vaccine, and has Johnson & Johnson stock and stock options. P. A. G. reports a patent for a COVID-19 monoclonal antibody from Aridis Pharmaceuticals. V. C. reports payments made to Emory University from Gilead Sciences. K. N. receives grants from NIH to participate in overall organization of COVID vaccine trials and for participation in vaccine trials and has a grant for Vaxco for a phase 1 testing of a broadly reactive COVID-19 vaccine. L. D. is an employee of Novavax, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults., Methods: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses., Results: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups., Conclusions: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223., Competing Interests: Potential conflicts of interest. S. G. is an employee of Sanofi Pasteur and C. A. D. G. was employed by Sanofi Pasteur at the time of the study. M. Ko. and O. V. D. M. are employees of GSK and hold shares in GSK. All other authors report no potential conflicts. Funding to pay the Open Access publication charges for this article was provided by the NIH. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Monovalent Omicron XBB.1.5-containing vaccines were approved for coronavirus disease 2019 (COVID-19) 2023-2024 immunizations., Methods: This ongoing, open-label, phase 2/3 study evaluated messenger RNA (mRNA)-1273.815 monovalent (50-µg Omicron XBB.1.5 spike mRNA) and mRNA-1273.231 bivalent (25-µg each Omicron XBB.1.5 and BA.4/BA.5 spike mRNAs) vaccines, administered as fifth doses to adults who previously received primary series, third doses of an original mRNA COVID-19 vaccine, and fourth doses of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity 29 days after vaccination are reported., Results: Participants (randomized 1:1) received 50-µg of mRNA-1273.815 (n = 50) or mRNA-1273.231 (n = 51); median intervals (interquartile range) from prior BA.4/BA.5 bivalent doses were 8.2 (8.1-8.3) and 8.3 (8.1-8.4) months, respectively. Fold increases in neutralizing antibody (nAb) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from prebooster nAb levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1, or D614G on day 29. Monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1, and JN.1 variants in a participant subset (n = 20) 15 days after vaccination. Reactogenicity was similar to that of mRNA-1273 vaccines., Conclusions: XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants, including JN.1, supporting the XBB.1.5-spike update for COVID-19 vaccines., Competing Interests: Potential conflicts of interest . S. C., N. M., B. G., D. K. E., K. W., A. N., D. L., L. E. A., J. F., W. D., J. M. M., and R. D. are employees of Moderna and may hold stock/stock options in the company. J. E. T. is a Moderna consultant. D. C. M. reports funding from Moderna for pseudovirus neutralization assays performed in the study. L. R. B. is a co–primary principal investigator of the COVE trial, funded by the National Institute of Allergy and Infectious Diseases and conducted in conjunction with Moderna. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer., Competing Interests: Potential conflicts of interest. The following list is a reflection of what has been reported to IDSA. To provide thorough transparency, IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors liaison to the Standards and Practice Guidelines Committee and, if necessary, the Conflicts of Interest and Ethics Committee. The assessment of disclosed relationships for possible conflicts of interest is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. L. B. receives research funding from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), Bill and Melinda Gates Foundation, Wellcome Trust, and Harvard Medical School; serves as chair of the Antimicrobial Drug Advisory Committee of the Food and Drug Administration; and is involved in HIV and COVID-19 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen Pharmaceuticals, Moderna, Military HIV Research Program, Bill and Melinda Gates Foundation, and the Ragon Institute. A. B. received an honorarium from the Institute for Clinical and Economic Review. V. C.-C. C. receives research funding from the Health and Medical Research Fund; serves on the Research Committee of the Society for Healthcare Epidemiology of America (SHEA); and serves on the international editorial boards for the Journal of Hospital Infection, Infection Prevention in Practice, and Antimicrobial Stewardship and Healthcare Epidemiology. K. M. E. serves as a scientific advisor for Merck, Bionet, IBM, Sanofi, X4 Pharmaceuticals, Inc, Seqirus, Inc, Moderna, Inc, GSK plc, Roche, and Pfizer; and receives research funding from the Centers for Disease Control and Prevention and the NIH. J. C. G. serves in an advisory role for Qpex, Shionogi, and Merck; receives research funding from Merck; previously served in an advisory role for Accelerate Diagnostics, Achaogen, Astellas Pharma, Melinta Therapeutics, Nabriva Therapeutics, Paratek Pharma, scPharmaceuticals, Spero Therapeutics, and Tetraphase Pharmaceuticals; and previously served on the speaker’s bureau for Astellas Pharma, Melinta Therapeutics, Merck, and Shionogi. R. T. G. serves as a panel member on the NIH COVID-19 Treatment Guidelines Panel; serves as the immediate Past Chair for the HIV Medicine Association; receives research funding from the NIH; and has served on the scientific advisory board for Gilead Sciences, Inc, and Merck. W. J. M. serves in an advisory role for Seqirus, Inc; receives research funding from Ansun Biopharma, Astellas Pharma, AstraZeneca, Eli Lilly and Company, Enanta Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Karius, Melinta Therapeutics, Merck, Moderna, Nabriva Therapeutics, Paratek Pharma, Pfizer, Roche, and Tetraphase Pharmaceuticals; and has previously received research funding from Abbott Laboratories. M. H. M receives research funding from the Agency for Healthcare Research and Quality, the Endocrine Society, and the Society for Vascular Surgery; serves as a Board member for the Evidence Foundation; has received research funding from the American Society of Hematology and the World Health Organization (WHO); and has served as a guideline methodologist for the WHO. R. A. M. receives research funding from the NIH, the WHO, the American College of Rheumatology, the American Society of Hematology, and Bohringer Ingelheim; serves as Chair of the Midwest Comparative Effectiveness Public Advisory Council of the Institute for Clinical and Economic Review (ICER); serves on the Methods Committee for Kidney Disease Improving Global Outcomes Work Group; serves on the Clinical Guidelines Committee for the Canadian Society of Nephrology; and previously served on the Clinical Guidelines Committee for the American College of Physicians (ACP). M. M. N. co-chairs the Pediatric Infectious Diseases Society COVID-19 Therapies Task Force, will receive support to attend as a speaker the American Academy of Pediatrics National Conference & Exhibition in October 2022, and has received research funding from Gilead Sciences. J. C. O. serves as an advisor for Bates College; holds stocks in Doximity, Inc; receives research funding from the MITRE Corporation and Nference, Inc; and serves on committees for the Society for Critical Care Medicine, SHEA, and University Lake School. R. W. S. served in an advisory role for GSK plc and Gilead Sciences. S. Soham serves in advisory roles for Amplyx Pharmaceuticals, Inc, ReViral Ltd, Adamis Pharmaceuticals, and Immunome; holds stocks in Immunome; receives research funding from Ansun BioPharma, Zeteo Tech, Inc, F2G, Emergent Biosolutions, Shionogi, Shire (now Takeda), Cidara Therapeutics, US Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Bloomberg Philanthropies, the State of Maryland, NIH/NIAID, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, HealthNetwork Foundation, Shear Family Foundation, Johns Hopkins University, and Mayo Clinic; serves as the Governor of the ACP; has received research funding from the University of Nebraska; and has served as an advisor for Janssen Pharmaceuticals, Acidophil, LLC, Adagio Therapeutics, Inc, Celltrion Healthcare, and Intermountain Health. A. H. S. receives research funding from the US Department of Veterans Affairs. S. Sultan serves on guideline panels for the American Gastroenterological Association (AGA) and receives research funding from the Department of Veterans Affairs Evidence Synthesis Program. Y. F.-Y. receives honoraria from the Evidence Foundation for evidence reviews and teaching, the AGA for evidence reviews, and ICER for committee meetings; serves as a Director for the Evidence Foundation and for the US GRADE Network; and served on an Independent Appraisal Committee for ICER. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost., Competing Interests: Potential conflicts of interest. A. R. B. has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, Moderna, Vaccine.co and Merck as well as consulting fees from Janssen and GSK. She serves as DSMB member for NIH, IDSA Public Health Committee. Honoraria as a speaker from Virology Education. L. R. B. has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for FDA. Dr Baden is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), Covid Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. D. J. D. has received a contract from Leidos Biomedical/NIH research to conduct the clinical trial through institution. A. R. F. has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, Moderna, Vaccine company and CyanVac through institution. Consultant fees from Arrow Pharmaceutical, ADMA biologics, GSK, and honoraria as a speaker from Sanofi and GlaxoSmithKline. Serves as DSMB advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline. S. E. F. has received funding from Leidos to Saint Louis University to conduct Protocol DMID 22-0004. Funding was also received to conduct the Moderna and Janssen trials phase 3 SARS-CoV-2 trials. Serves as DSMB for HVTN Safety Monitoring Board. D. N. F. has as a contract from CDC and is the site PI for DN Fusco study of COVID in Special Populations. D. N. F. served on an HBV Advisory board for Gilead related to hepatitis C & B viruses and Axcella related to Long COVID. P. A. G. has received funding from NIH. PAG has a patent for COVID-19 monoclonal not developed clinically and received consulting fees from International AIDS Society as speaker. L. C. I. has received support from NIH, Moderna, Pfizer, and Sanofi. L. C. I. has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, Pediatric Emergency Medicine Associates, and NIH/NLM/National Institute on Minority Health and Health Disparities as well as consulting fees from Moderna. L. C. I. has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, Moderna, CDC and American Academy of Pediatrics- Georgia Chapter. L. C. I. Serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and CoVID-19 Task Force, Georgia. L. C. I. has a leadership role Break the Cycle of Health Disparities Inc, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). L. C. I. has received travel/meeting support from the American Academy of Pediatrics and Moderna. L. A. J. has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. L. A. J. also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials. S. K. has received research grants from NIH, Pfizer, U.S. Centers for Disease Control and Prevention, Meisa, Emergent BioSolutions. S. K. also received support from American Academy of Pediatrics as speaker. A. C. K. has received research support from COVID-19 Adaptive Variance Immunologic Landscape Trial # 28C15000NYUPG266894. S. J. L. has received NIH grants through institution. Consulting fees from Hookipa Pharma. A. F. L. has received grants from Merck, Gilead and, GSK through institution as well as consulting fees from Vir Biotechnology. A. F. L. has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, Cepheid and medication donated by Mayne Pharma to support research study. M. M. has received funding from Emmes through NIH contract # HHSN272201500002C. L. J. M. has received funding from Emmes through NIH contract # HHSN272201500002C. D. C. M. has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines. J. M. has received funding from Division of Microbiology and Infectious Diseases, contract # 75N93021C00012. A. N. has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01. R. M. N. has received grants from NIAID-DMID and travel/meeting support from Moderna. C. M. P. has received funding from NIAID UM1AI148684. R. M. P. has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna and NIH through institution. N. G. R. has received research grants from NIH, Pfizer, Merck, Sanofi, Quidel, Immorna, Vaccine Company and Lilly through her institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi and Moderna. N. G. R. serves as DSMB on safety committees for ICON, Micron and EMMES and is a member of the Moderna, Sanofi, Seqirus and Pfizer selected Advisory boards. Plays leadership advisory role for ARLG, TMRC, CDC-Pertussis challenge, Clinical Infectious Diseases. Equipment supports from Georgia Research Alliance. D. J. S. has received support from NIH-NIAID CEIRR, grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings. K. T. has received funding from Emmes through NIH contract # HHSN272201500002C. E. B. W. has received funding from Leidos Biomedical Research AGREEMENT NO. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. E. B. W. has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. E. B. W. serves as member of Vaxcyte Scientific Advisory board. P. L. W. has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. P. L. W. has also received consulting fees from Pfizer and serves on DSMB advisory board for Emmes Corporation, Blue Lake. M. B. has received research grants from Leidos Biomedical Research and Pfizer through institution. J. A. W. has received funding from NIH-DMID 75N91019D00024. R. L. A., T. M. B., S. M. M., M. K. M., J. H. B., S. C., C. L., P. C. R., R. R. authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While the coronavirus disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute convened a think tank with thought leaders from academia, clinical practice, the pharmaceutical industry, patient advocacy, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Disease Control and Prevention to share, firsthand, expert knowledge of the insights gained from the COVID-19 pandemic and how this acquired knowledge can help inform the next pandemic response. The think tank focused on pandemic preparedness, therapeutics, vaccines, and challenges related to clinical trial design and scale-up during the early phase of a pandemic. Based on the multi-faceted discussions, we outline 10 key steps to an improved and equitable pandemic response., Competing Interests: Potential conflicts of interest. A. F. H. reports contracts with Pfizer and Merck and consulting fees from Merck. B. L. is an employee of and owns stock in Moderna and reports support for travel to a meeting from Moderna. C. W. W. reports consulting fees from Arena Pharmaceuticals, BioFire, FHI Clinical, Giner, Karius, and SeLux Diagnostics; grants or contracts (paid to institution) from Defense Advanced Research Projects Agency, National Institutes of Health (NIH)-Antibacterial Resistance Leadership Group/National Institute of Allergy and Infectious Diseases/NIH Vaccine and Treatment Evaluation Units/National Institute of Mental Health/National Institute of General Medical Sciences, Sanofi, Najit, the Centers for Disease Control and Prevention (CDC), Patient-Centered Outcomes Research, United States Army Medical Research Acquisition Activity, Department of Defence, Abbott, and Pfizer; support for attending meetings and/or travel from the American Society for Microbiology (ASM); participation on a data and safety monitoring board (DSMB) or advisory board for IDbyDNA, Janssen, Regeneron, Roche Molecular Sciences; a leadership or fiduciary role for ASM and the American Society of Tropical Medicine and Hygiene; being employed by Duke University, Durham Veterans Affairs Hospital, Biomeme, and Equity/Founder of Predigen, Inc; and planned, issued, or pending patents for biomarkers for the molecular classification of bacterial infection, methods to diagnose and treat acute respiratory infections, gene expression signatures useful to predict or diagnose sepsis and methods of using the same, host-based molecular signatures of human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 (coronavirus disease 2019 [COVID-19]), methods of identifying infectious disease and assays for identifying infectious disease, and nasopharyngeal protein biomarkers of acute respiratory virus infection and methods of using same. H. C. and S. C. B. are employees of and hold or may hold stock in AstraZeneca. J. W. reports being an employee of and owns stock/stock options in and received equipment, materials, drugs, medical writing, gifts, and other services from Johnson & Johnson and, as CMO, has been deposed in litigation; patents issued that do not relate to the current article (available on request); and a role on the Brooklyn College Cancer Center Advisory Board, a Brooklyn College Foundation Trustee, and on the Fellowships at Auschwitz for the Study of Professional Ethics, Academic Committee. J. R. D. is an employee and shareholder in Eli Lilly and Company. L. H. C. reports consulting fees from Regeneron for the NFL Players Association and grants or contracts from NIH for PCORI. L. S. reports stock/stock options in Novartis. L. R. is an employee of and owns stock/stock options in and received support for attending meetings and/or travel from Bayer AG. M. S. reports consulting fees from AbbVie, Assembly Bio, Antios, Arbutus, Gilead Sciences, Precision Bio, and GSK for scientific advisory boards and participation on a DSMB for Gilead Sciences and AbbVie and a role as editor of the Journal Viral Hepatitis. O. V. is an employee of Boehringer Ingelheim. P. P. has a patent pending for sotrovimab and is an employee and shareholder of Vir Biotechnology. S. N. reports consulting fees from Pardes Biosciences, Theratechnologies, and Silverback Therapeutics; stock/stock options in Vir Biotechnology; grants or contracts (paid to institution) from Gilead Sciences and AbbVie; participation on an advisory board for Vir Biotechnology, a DSMB for Personal Health Insights, Inc; and serving on an event adjudication committee for Bristol–Myers Squibb/PRA. M. A. M. reports consulting fees from Abcam; stock/stock options in Grid Therapeutics; a role as an advisory board member for GSK Belimumab Pregnancy Registry; and funding to Duke from NIAD (U01 AI151378): Centers for Research in Emerging Infectious Disease (CREID) Network Coordinating Center, HHS 75N93019C00050: Duke Collaborative Influenza Vaccine Innovation Centers (CIVICs) A: Vaccine Center, HHS 75N93019C00054: Duke CIVICs C: Clinical Core, U19 AI144177: A Global Syphilis Vaccine Targeting Outer Membrane Proteins Of Treponema pallidum, 2P01 AI089618: Structure-Function Analysis Of Infection- And Vaccine-Induced B Cell Repertoires. S. E. T. reports royalties from UptoDate; grants or contracts (paid to institution) from the CDC; payment or honoraria (to author) from the Infectious Disease Society of America (IDSA) and Emerson Hospital; support from DCRI to attend the meeting upon which this article was based. L. R. B. is involved in human immunodeficiency virus (HIV) and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen, Moderna, Military HIV Research Program, the Gates Foundation, and Harvard Medical School. reports participation on a DSMB for NIH and AMDAC Committee for the FDA (research funded by the NIH, Welcome Trust, and the Gates Foundation). R. T. G. reports a leadership or fiduciary role on the NIH COVID Treatment Guidelines Panel and IDSA COVID Treatment Guidelines Panel. R. G. reports grants (to institution) from NIH/NIAID, book chapter royalties from Elsevier, and section editor royalties from UpToDate. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines., Competing Interests: Potential conflicts of interest. E. J. A. has received grants from Pfizer, Moderna, Janssen, GSK, Sanofi, Micron, and Regeneron through institution as well as consulting fees from Pfizer, Janssen, Moderna, and Sanofi. E. J. A. serves on safety/advisory boards for Sanofi, ACI Clinical/WCG and Kentucky Bioscience, Inc. A. R. B. has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, and Merck as well as consulting fees from Janssen and GSK. L. R. B. has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for Food and Drug Administration (FDA). L. R. B. is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. D. J. D. has received a contract from Leidos Biomedical research to conduct the clinical trial through institution. A. R. F. has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, and CyanVac through institution, consultant fees from Arrowhead and Icosavax, and honoraria as a speaker from Moderna and GlaxoSmithKline. A. R. F. also serves on safety/advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline. S. E. F. has received funding from Leidos to Saint Louis University to conduct Protocol DMID22-0004. D. N. F. has as a contract from Centers for Disease Control and Prevention (CDC) and is the site principal investigator (PI) for clinical trials from Gilead, Regeneron, and MetroBiotech, LLC. She is the PI on 1 investigator-initiated award from Gilead and the co-PI on another investigator-initiated award from Gilead. D. N. F. served on an HBV Advisory board for Gilead in 2021 and received payment for expert testimony not related to COVID in 2022. P. A. G. has received funding for COVAIL clinical trial. P. A. G. has also received consulting fees from Janssen Vaccines. L. C. I. has received support for the present manuscript from NIH-NIAID/DMID, Moderna, Pfizer, and Sanofi. L. C. I. has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, AHRQ, and NIH/NLM/NIMHD as well as consulting fees from Moderna, CDC, and Pediatric Emergency Medicine Associates, LLC. L. C. I. has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, and American Academy of Pediatrics- Georgia Chapter. L. C. I. serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and COVID-19 Task Force, Georgia. L. C. I. has a leadership role in the Pediatric Infectious Disease Society, serves as board member on the Emory University- Pediatric and Reproductive Environmental Health Scholars-Southeastern, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). L. C. I. has received travel/meeting support from the American Academy of Pediatrics and Moderna. L. A. J. has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. L. A. J. also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials. S. J. L. has received NIH grants through institution. A. F. L. has received grants from Merck, Gilead, and ViiV through institution as well as consulting fees from Vir Biotechnology. A. F. L. has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, and medication donated by Mayne Pharma to support research study. M. M. has received funding from Division of Microbiology and Infectious Diseases for contract number 75N93021C00012. D. C. M. has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines. J. M. has received funding from Division of Microbiology and Infectious Diseases, contract number 75N93021C00012. A. N. has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01. R. M. N. has received grants from Moderna and Janssen and travel/meeting support from Moderna. C. M. P. has received funding from NIAID UM1AI148684. R. M. P. has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna, and NIH through institution. N. G. R. has received research grants from Pfizer, Merck, Sanofi, Quidel, and Lilly through institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi. N. G. R. serves on safety committees for ICON and EMMES and is a member of the Moderna Advisory board. D. J. S. has received support from NIH-NIAID CEIRR, grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings. K. T. has received funding from Division of Microbiology and Infectious Diseases contract number 75N93021C00012. E. B. W. has received funding from Leidos Biomedical Research agreement number. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. E. B. W. has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. E. B. W. serves as member of Vaxcyte Scientific Advisory board. P. L. W. has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. P. L. W. has also received consulting fees from Pfizer and serves on safety/advisory board for Emmes Corporation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective., Competing Interests: Potential conflicts of interest. E. M. B. reports personal fees and non-financial support from Terumo BCT, Abbott Laboratories, Tegus and UptoDate, outside of the submitted work. K. G. receives support from UptoDate, Teach for America and the Aspen Institute. E. M. B. is a member of the US Food and Drug Administration (FDA) Blood Products Advisory Committee. Any views or opinions that are expressed in this manuscript are those of the author's, based on his own scientific expertise and professional judgment; they do not necessarily represent the views of either the Blood Products Advisory Committee or the formal position of FDA, and do not bind or otherwise obligate or commit either Advisory Committee or the Agency to the views expressed. E. M. B. also reports that his time is funded in part by NHLBI through grant number 1K23HL151826; receives royalties for an article on convalescent plasma from UpToDate; consulting fees from California Institute for Regenerative Medicine as an advisor on convalescent plasma program; and served as an unpaid, invited member for a Data Safety Monitoring Board for the following trial: “Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda: A Phase III randomized controlled trial.” A. C. reports grants or contracts with the NIH, unrelated to this work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Bristo-Myers Squibb, Ortho Diagnostics; participation on a Data Safety Monitoring Board or Advisory Board for Bristo-Myers Squibb and SAB Therapeutics; a leadership or fiduciary role on COVID-19 Convalescent Plasma Project; and stock or stock options from SAB Therapeutics. R. K. A. reports study grant support paid to institution from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire. M. J. J. reports grants or contracts from BARDA UL1TR002377, Octapharma, NBA, Millennium Pharma, United Health Group, Mayo Clinic; consulting fees from California Regenerative Medicine City of Hope. K. G. reports grants or contracts unrelated to this work made to institution (grant number NCATS KL2TR0030099); royalties or licenses as an Uptodate author; consulting fees to author from Aspen Institute, Teach for America, and Spark Healthcare; participation on a Data Safety Monitoring Board or Advisory Board as an unpaid advisor to Pfizer to increase access to Paxlovid. R. R. R. reports funds to institution from Roche, Regeneron, and Gilead; consulting fees from Roche and Merck; participation on a Data Safety Monitoring Board or Advisory Board for Novartis and Allovir; and a role as Board member of American Society of Transplantation. E. M. B. reports that his time is funded in part by NHLBI through grant number 1K23HL151826; receives royalties for an article on convalescent plasma from UpToDate; consulting fees from California Institute for Regenerative Medicine as an advisor on convalescent plasma program; and served as an unpaid, invited member for a Data Safety Monitoring Board for the following trial: “Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda: A Phase III randomized controlled trial.” S. S. reports grants or contracts made to institution from US Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Shionogi, Shire, Ansun, Cidara, Zeteo Tech Inc, F2G, Emergent Biosolutions, Bloomberg Philanthropies, the State of Maryland, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, Shear Family Foundation, HealthNetwork Foundation, Mayo Clinic, University of Nebraska; consulting fees made directly to author from Immunome, Adagio Therapeutics, Celltrion Healthcare, Karius; payment or honoraria to author for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Prime Inc and Peerview; travel support from Peerview for American Transplant Congress 2022, from NCCN for NCCN Guideline meeting, and from ACP for ACP board of governors meeting; paid participation on a Data Safety Monitoring Board or Advisory Board for Intermountain Health, Karyopharm, Adamis Health; a role on guideline panels for NCCN, IDSA, MSG/EORTC, on RSV vaccine workgroup for ACIP/CDC, as Governor of Washington D.C. Chapter of ACP, and as member of Board of Governors of ACP; stock or stock options from Immunome. L. R. B. reports grants to institution from NIH/Harvard Medical School, Wellcome Trust, Bill and Melinda Gates Foundation; participation on DSMB for NIH and AMDAC for FDA; and is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Bill and Melinda Gates Foundation, and Harvard Medical School. P. T. reports Horizon 2020 EU Grant SUPPORT-e to institution; unpaid role as President, European Blood Alliance (association of not-for-profit blood establishments in Europe); and employment by the Etablissement Français du Sang (French transfusion public service in charge of collecting, manufacturing; testing and issuing blood components in France). D. S. reports grants or contracts from US Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number W911QY2090012), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) 3R01AI152078-01S1, Bloomberg Philanthropies, NIH National Center for Advancing Translational Sciences (NCATS) U24TR001609, State of Maryland, Division of Intramural Research NIAID NIH, Mental Wellness Foundation, HealthNetwork Foundation, Octapharma, ZonMw, the Netherlands (10430062010001), Shear Family Foundation, Sanquin Blood Supply, Fight AIDS and Infectious Diseases Foundation (Badalona, Spain), Grifols Worldwide Operations (Dublin, Ireland), Crowdfunding campaign, YoMeCorono, Hospital Universitari Germans Trias i Pujol, Banc de Sang i Teixits de Catalunya, Bill and Melinda Gates Foundation, Fundación INFANT Pandemic Fund, National Heart, Lung, and Blood Institute (NHLBI) (grant numbers 1OT2HL156812-01, U24NS100659, and U24NS100655), National Institute of Neurological Disorders and Stroke of the National Institutes of Health, NIH/NIAID R01AI150763 Dual artemisinin action combats resistance, NIH R21TR001737 Quantum model repurposing of cethromycin for liver stage malaria, NIH R01AI111962 Optimized Combination Antimalarial Drug Therapy, DoD TB210115. CDMRP Tick-Borne Disease Research Program. A Pharmacokinetic and Pharmacodynamic Immunocompromised Mouse Model of the Human Tick-Borne Disease Babesia microti; royalties or licenses from Binax Inc/D/B/A Inverness Medical for plasmids for HRP aldolase for malaria diagnostic test; the following patents: Issued-USP 9,642,865 9 May 2017 New angiogenesis inhibitors, Issued-USP 9,568,471 14 February 2017 Malaria Diagnosis in Urine, Issued-USP 7,270,948 18 September 2007 Detection of malaria parasites by laser desorption mass spectrometry, Pending SALTS AND POLYMORPHS OF CETHROMYCIN FOR THE TREATMENT OF DISEASE Patent Application (Application number 20210163522), Pending- Macrolide compounds and their use in liver stage malaria and related disease Application PCT/US2015/046665, and participation on 2018 NIAID SMC/ISM Intramural; role as AliquantumRx Founder and Board member (macrolide for malaria). C. C. reports institutional payment from 1 NIH: PassItOn A trial of COVID convalescent plasma (Project Dates: 9/2020–10/2020); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo; support for attending meetings and/or travel from Department of Lab Medicine and Pathology, University of Minnesota, Association for the Advancement of Blood and Biotherapies (AABB), and Biomedical Excellence for Safer Transfusion (BEST collaborative); participation on OrthoClinical Diagnostics Advisory Board; role as Chief Medical Officer, Association for the Advancement of Blood and Biotherapies (AABB) (salaried part time employee). V. D. reports grants or contracts to institution from AlloVir and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Invivyd to author. J. P. H. reports participation on Scientific Advisory Board for Immunome, Inc, regarding development of COVID-19 monoclonal antibodies, role on leadership group, unpaid, for the National Convalescent Plasma Project Advocacy Group; and stock options for Immunome, Inc, related to participation on scientific advisory board. C. S. O. reports unpaid roles as Regional Director for ISBT and Chair ISBT convalescent working group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV., Methods: This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo. Primary end points were safety and antibody responses., Results: In total 152/155 participants (clade C, n = 26; bivalent protein, n = 103; placebo, n = 26) received ≥1 injection. The highest adverse event (AE) severity was grade 3 (local pain/tenderness, 12%, 2%, and 0% of the respective groups; solicited systemic AEs, 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79 595 ELISA units (EU)/mL and 137 520 EU/mL in the clade C and bivalent protein groups (P < .001) after dose 4 and 16 862 EU/mL and 25 162 EU/mL 6 months later. Antibody response breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group., Conclusions: Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses. Clinical Trials Registration. NCT02935686., Competing Interests: Potential conflicts of interest. D. H. B. reports grants from Janssen Vaccines and Prevention outside the submitted work, as well as an HIV vaccine patent licensed to Janssen Vaccines and Prevention. S. S. reports grants from the National Institutes of Health (NIH) and HIV Vaccine Trials Network (HVTN) during the conduct of the study. J. H. reports grants from the NIH and HVTN during the conduct of the study; and support for travel to attend meetings from HVTN outside the submitted work. G. D. T. reports grants from the NIH during the conduct of the study; consulting fees from Janssen Vaccine and Prevention, Axon Pharma, and Gilead Sciences outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, or manuscript writing/educational events from the University of North Carolina Scientific Advisory Board, the NIH Board of Scientific Counselors, and Johns Hopkins University; and support for attending meetings/travel from the NIH and Gates travel. J. G. K. reports grants from the NIH during the conduct of the study. M. J. M. reports grants from the National Institute of Allergy and Infectious Diseases (NIAID; funding for Seattle CTU Grant and funding for HVTN Lab) during the study. K. W. C. reports grants from NIH, NIAID during the conduct of this study. S. C. D. reports grants from the NIH and Gates Foundation during the conduct of the study; and a contract from Janssen Vaccines and Prevention outside the submitted work. G. A. reports grants from the NIH, Gates Foundation, Sanofi, Moderna, Pfizer, Janssen, Abbvie, Medicago, Gilead Sciences, and GSK during the conduct of the study; grants from BioNTech, Merck, and Bristol Myers Squibb outside the submitted work; consulting fees from Sanofi and Moderna; payment or honoraria for lectures, presentations, speakers bureaus, or manuscript writing/educational events from GSK and AstraZeneca; a patent pending for REFORM-Antibody Engineering (MGH); participation in a data safety monitoring board (DSMB) for CAPRISA CAP276 HIV monoclonal; leadership in a scientific advisory board for Sanofi; and stock or stock options in Systems Seromyx and Leyden Labs. G. F. reports grants from the NIH during the conduct of the study; and grants from the NIH outside the submitted work. D. M. reports grants from HVTN during the conduct of the study. P. M. reports holding stock/stock options in CureVac outside the submitted work. P. A. G. reports grants from the NIH outside the submitted work; and consulting fees from Johnson and Johnson. S. E. reports grants from HVTN and Janssen Vaccines and Prevention during the study; and grants from Sanofi outside the submitted work. M. S. S. reports grants from the NIH during the conduct of the study. L. R. B. reports grants from the NIH during the conduct of the study; grants from the NIH (Harvard Medical School), Bill and Melinda Gates Foundation, and Wellcome Trust outside the submitted work; participation in a DSMB for the NIH; participation in an advisory board for the Food and Drug Administration, and involvement in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HVTN, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Janssen Vaccines and Prevention, Moderna, Military HIV Research Program, Bill and Melinda Gates Foundation, and Harvard Medical School. S. R. W. reports grants from Janssen Vaccines and Prevention and from NIH-NIAID during the conduct of the study; grants from Sanofi Pasteur, ModernaTx, Vir Biotechnology, and Worcester HIV Vaccine outside the submitted work; participation in a DSMB or advisory board for Janssen Vaccines and Prevention; and other financial or nonfinancial interests with Regeneron Pharmaceuticals (spouse employment and stock/stock options). D. J. S., C. C., M. S., K. C., M. G. P., H. S., and F. T. are employees of Janssen and hold Johnson and Johnson stock. S. N. is an employee of Janssen. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The reactogenicity and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines are well studied. Little is known regarding the relationship between immunogenicity and reactogenicity of COVID-19 vaccines., Methods: This study assessed the association between immunogenicity and reactogenicity after 2 mRNA-1273 (100 µg) injections in 1671 total adolescent and adult participants (≥12 years) from the primary immunogenicity sets of the blinded periods of the Coronavirus Efficacy (COVE) and TeenCOVE trials. Associations between immunogenicity through day 57 and solicited adverse reactions (ARs) after the first and second injections of mRNA-1273 were evaluated among participants with and without solicited ARs using linear mixed-effects models., Results: mRNA-1273 reactogenicity in this combined analysis set was similar to that reported for these trials. The vaccine elicited high neutralizing antibody (nAb) geometric mean titers (GMTs) in evaluable participants. GMTs at day 57 were significantly higher in participants who experienced solicited systemic ARs after the second injection (1227.2 [1164.4-1293.5]) than those who did not (980.1 [886.8-1083.2], P = .001) and were associated with fever, chills, headache, fatigue, myalgia, and arthralgia. Significant associations with local ARs were not found., Conclusions: These data show an association of systemic ARs with increased nAb titers following a second mRNA-1273 injection. While these data indicate systemic ARs are associated with increased antibody titers, high nAb titers were observed in participants after both injections, consistent with the immunogenicity and efficacy in these trials. These results add to the body of evidence regarding the relationship of immunogenicity and reactogenicity and can contribute toward the design of future mRNA vaccines., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Messenger RNA (mRNA)-1273 vaccine demonstrated 93.2% efficacy against coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial. The humoral immunogenicity results are now reported., Methods: Participants received 2 mRNA-1273 (100 µg) or placebo injections, 28 days apart. Immune responses were evaluated in a prespecified, randomly selected per-protocol immunogenicity population (n = 272 placebo; n = 1185 mRNA-1273). Serum binding antibodies (bAbs) and neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike protein were assessed at days 1, 29, and 57 by baseline SARS-CoV-2-negative (n = 1197) and SARS-CoV-2-positive (n = 260) status, age, and sex., Results: SARS-CoV-2-negative vaccinees had bAb geometric mean AU/mL levels of 35 753 at day 29 that increased to 316 448 at day 57 and nAb inhibitory dilution 50% titers of 55 at day 29 that rose to 1081 at day 57. In SARS-CoV-2-positive vacinees, the first mRNA-1273 injection elicited bAb and nAb levels that were 11-fold (410 049) and 27-fold (1479) higher than in SARS-CoV-2-negative vaccinees, respectively, and were comparable to levels after 2 injections in uninfected participants. Findings were generally consistent by age and sex., Conclusions: mRNA-1273 elicited robust serologic immune responses across age, sex, and SARS-CoV-2 status, consistent with its high COVID-19 efficacy. Higher immune responses in those previously infected support a booster-type effect. Clinical Trials Registration. NCT04470427., Competing Interests: Potential conflicts of interest. L. R. B., H. M. E., R. R., and S. S. report grants from NIH and/or NIAID during the conduct of the study. D. M. and A. M. disclose research funding from Moderna. R. P., Y. D. P., B. G., A. A., W. D., H. Z., and B. L. report being employees of Moderna, Inc. and may hold stock/stock options in the company. J. E. T. is a Moderna consultant. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine-induced humoral response and reactogenicity profile are described in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Findings showed that 75.0% (by Simoa assay) or 80.0% (by Roche assay) of the HSCT cohort had a positive antibody response on series completion, compared with 100% in the healthy cohort., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Vaccine clinical trials have been essential to developing effective severe acute respiratory syndrome coronavirus 2 vaccines. The challenges of supply chain disruptions, infection control, study designs, and participant factors that affect trial procedures are reviewed, with specific solutions to streamline the clinical trial process., Competing Interests: Potential conflicts of interest. A. C. S. is involved in human immunodeficiency virus (HIV), coronavirus disease 2019 (COVID-19) and other vaccine clinical trials conducted in collaboration with the National Institutes of Health (NIH), the HIV Vaccine Trials Network, the COVID Vaccine Prevention Network (CoVPN), the International AIDS Vaccine Initiative, Crucell/Janssen, Moderna, and Sanofi. N. R. is the international cochair for the Sanofi COVID-19 vaccine efficacy trial (CoVPN 3005), the site principal investigator for CoVPN 3001, and a CoVPN member. N. R. also serves on safety committees for ICON and Emmes, and N. R.’s institution receives funding from Quidel, Merk, Pfizer, and Lilly. L. R. B. is involved in HIV, COVID-19, and other vaccine clinical trials conducted in collaboration with the NIH, the HIV Vaccine Trials Network, CoVPN, the International AIDS Vaccine Initiative, Crucell/Janssen, Moderna, the Military HIV Research Program, the Gates Foundation, and the Ragon Institute. L. R. B. has also received funding from NIH, the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, Wellcome Trust, and the Gates Foundation, in addition to holding data and safety monitoring board or advisory board positions with the NIH and Food and Drug Administration. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The impact of coronavirus disease 2019 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of severe acute respiratory syndrome coronavirus 2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, the higher cycle thresholds, repeat negative tests, and inability to culture virus raise questions about their clinical significance., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. Eleven of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of immunoglobulin G (IgG) and immunoglobulin A (IgA)., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment., Methods: We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples., Results: The Roche assay registered the highest specificity 99.6% (3/832 false positives), the Ragon/MGH assay 99.5% (4/832), the primary Simoa assay model 99.0% (8/832), and the Epitope IgG and IgM 99.0% (8/830) and 99.5% (4/830), respectively. Overall sensitivities for the Simoa, Roche pan-IG, Epitope IgG, Ragon/MGH IgG, and Epitope IgM were 92.0%, 82.9%, 82.5%, 64.5% and 47.0%, respectively. The Simoa immunoassay demonstrated the highest sensitivity among samples stratified by days postsymptom onset (PSO), <8 days PSO (57.69%) 8-14 days PSO (93.51%), 15-21 days PSO (100%), and > 21 days PSO (95.18%)., Conclusions: All assays demonstrated high to very high specificities while sensitivities were variable across assays., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There were no cases of tuberculosis in a cohort of 2531 patients who underwent hematopoietic cell transplantation from 2010 to 2015 after 7323 person-years of follow up (95% confidence interval [CI], 0.0-0.05 cases/100 person-years), including 29 (1.15%) patients with untreated latent tuberculosis after 89 person-years of follow-up (95% CI, 0.0-4.06 cases/100 person-years)., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains., Methods: This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365., Results: All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine., Conclusions: No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited., Clinical Trials Registration: NCT02218125.

Viral infections have been reported with dasatinib use, but its cytomegalovirus risk after hematopoietic-cell transplantation (HCT) is not known. We found that post-HCT dasatinib use increased the risk of cytomegalovirus reactivation (adjusted hazard ratio, 7.65; 95% confidence interval, 1.84-31.7), controlling for acute graft-versus-host disease, in 109 patients with Philadelphia-chromosome-positive malignancies., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections., Patients and Methods: A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared., Results: Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively., Conclusions: Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both., Methods: A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen., Results: T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI], .6-1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively)., Conclusions: These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized., Clinical Trials Registration: NCT01095224., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases.

Background: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans., Methods: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed., Results: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry., Conclusions: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation., Clinical Trials Registration: NCT01103687., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection., Methods: Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples., Results: The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%)., Conclusions: In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA., Methods: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed., Results: Self-limited reactogenicity was observed after the initial immunization in the highest (10(11) vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 10(9), 10(10), and 10(11) vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5., Conclusions: Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions. Clinical Trials Registration. NCT00695877., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses., Methods: A total of 299 individuals received 2 doses of JS7 DNA vaccine and 2 doses of MVA/HIV62B at 0, 2, 4, and 6 months, respectively (the DDMM regimen); 3 doses of MVA/HIV62B at 0, 2, and 6 months (the MMM regimen); or placebo injections., Results: At peak response, 93.2% of the DDMM group and 98.4% of the MMM group had binding antibodies for Env. These binding antibodies were more frequent and of higher magnitude for the transmembrane subunit (gp41) than the receptor-binding subunit (gp120) of Env. For both regimens, response rates were higher for CD4(+) T cells (66.4% in the DDMM group and 43.1% in the MMM group) than for CD8(+) T cells (21.8% in the DDMM group and 14.9% in the MMM group). Responding CD4(+) and CD8(+) T cells were biased toward Gag, and >70% produced 2 or 3 of the 4 cytokines evaluated (ie, interferon γ, interleukin 2, tumor necrosis factor α, and granzyme B). Six months after vaccination, the magnitudes of antibodies and T-cell responses had decreased by <3-fold., Conclusions: DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens. Methods to increase the immunogenicity of DNA vaccines are needed., Methods: HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX®-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools., Results: Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination., Conclusions: Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.

Purpose: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated., Methods: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data., Results: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup., Conclusion: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.

Background: Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important., Methods: We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28. Twenty-four hematopoietic stem cell transplant recipients were enrolled sequentially into the study, and vaccine or placebo was administered under a randomized, double-blind allocation. Ten subjects received vaccine containing 10(7) median tissue culture infective doses (TCID50) of MVA-BN, 10 subjects received vaccine containing 10(8) TCID50 of MVA-BN, and 4 subjects received placebo., Results: MVA-BN was generally well tolerated at both doses. No vaccine-related serious adverse events were identified. Transient local reactogenicity was more frequently seen at the higher dose. Neutralizing antibodies (NAb) to Vaccinia virus (VACV) were elicited by both doses of MVA-BN and were greater for the higher dose. Median peak anti-VACV NAb titers were 1:49 in the lower-dose group and 1:118 in the higher-dose group. T-cell immune responses to VACV were detected by an interferon γ enzyme-linked immunosorbent spot assay and were higher in the higher-dose group., Conclusions: MVA-BN is safe, well tolerated, and immunogenic in HSCT recipients. These data support the use of 10(8) TCID50 of MVA-BN in this population., Clinical Trials Registration: NCT00565929.

Background: Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans., Methods: Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays., Results: We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study., Conclusion: Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector., Clinical Trials Registration: NCT00618605.

Background: We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans., Methods: Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed., Results: Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively., Conclusion: This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1., Clinical Trials Registration: NCT00618605.

Background: We assessed the morbidity of herpesviruses in patients with type 1 diabetes mellitus (T1D) enrolled in immunosuppressive treatment studies., Methods: Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) infections were monitored in 126 participants of a randomized, double-blind, placebo-controlled study of daclizumab (DZB) and mycophenolate mofetil (MMF) including DZB(+)MMF(+), DZB(-)MMF(+), DZB(+)MMF(-), and DZB(-)MMF(-). During the 2-year follow-up, herpesviral infections were monitored clinically, by serology and blood DNA polymerase chain reaction., Results: Among 57 baseline EBV-seronegative participants, 9 developed EBV primary infections, including 2 with infectious mononucleosis syndrome. There were no appreciable differences in the course of the primary EBV infections across treatment groups. Among 69 baseline EBV-seropositive participants, 22 had virologic reactivations, including 1 symptomatic DZB(-)MMF(+) subject. Compared with 7 DZB(-)MMF(-) EBV reactivators, the 9 DZB(+)MMF(+) reactivators tended to have more prolonged viremia (11.4 vs 4.4 months; P = .06) and higher cumulative viral burden (14.2 vs 12.5 log EBV copies/mL; P = .06). Four of 85 baseline CMV-seronegative subjects developed asymptomatic primary CMV infections. There were no CMV reactivations. Of 30 baseline HSV-seropositive subjects, 8 developed ≥1 episode of herpes labialis; 1 subject had a primary HSV infection; and 1 subject without baseline serology information had a new diagnosis of genital HSV. There were no significant differences in the incidence of HSV recurrences across treatment groups. Of 100 baseline VZV-seropositive subjects, 1 DZB(-)MMF(-) subject developed herpes zoster and 1 DZB(-)MMF(+) subject had Bell's palsy possibly related to VZV., Conclusions: The use of DZB alone or in combination with MMF was not associated with increased morbidity due to herpesviruses., Clinical Trials Registration: NCT00100178.

Background: To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig)., Methods: This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5)., Results: No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) γ and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/10⁶ peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/10⁶ PBMCs (P = .003; T4 vs T5) for the IFN-γ ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4., Conclusions: Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies., Clinical Trials Registration: NCT00069030.

Background: Recombinant DNA and modified vaccinia virus Ankara (rMVA) vaccines represent a promising approach to an HIV/AIDS vaccine. This Phase 1 clinical trial compared the safety and immunogenicity of a rMVA vaccine administered with and without DNA vaccine priming, Methods: GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants., Results: Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM., Conclusions: MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.

We describe 3 cases of invasive fungal disease in the setting of transplantation-associated immunosuppression, developing months to years after clinically resolved penetrating soft-tissue injuries with wood fragments. Invasive fungal disease resulting from remote inoculation is a distinct syndrome in immunocompromised patients presenting with soft-tissue abnormalities in areas of prior trauma.

Background: We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration., Methods: Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart., Results: MVA was generally well tolerated at all dose levels and by all routes. More pronounced local reactogenicity was seen with the intradermal and subcutaneous routes than with intramuscular administration. Binding antibodies to whole virus and neutralizing antibodies to the intracellular mature virion and extracellular enveloped virion forms of vaccinia virus were elicited by all routes of MVA administration and were greater for the higher dose by each route. Similar levels of neutralizing antibodies were seen at a 10-fold-lower dose given intradermally (1 x 10(7) median tissue culture infective doses [TCID(50)]), compared with responses after 1 x 10(8) TCID(50) given intramuscularly or subcutaneously. T cell immune responses to vaccinia virus were detected by an interferon gamma enzyme-linked immunospot assay but had no clear relationship to dose or route., Conclusions: These data suggest that intradermal immunization with MVA provides a dose-sparing effect by eliciting antibody responses similar in magnitude and kinetics to those elicited by the intramuscular or subcutaneous routes but at a 10-fold-lower dose.

Background: Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax)., Methods: Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization. Subjects were followed up for clinical take, viral shedding, and immune responses., Results: MVA administration attenuated clinical takes in 21 (72%) of 29 subjects, compared with 0 of 7 placebo recipients (P = .001). Attenuation was most significant in MVA groups that received 1 x 10(7) median tissue culture infective doses (TCID(50)) intradermally (P = .001) and 1 x 10(7) TCID(50) intramuscularly (P = .001). Both duration and peak titer of viral shedding were reduced in MVA recipients. Peak neutralizing antibody responses to vaccinia virus or MVA previously induced by MVA immunization were associated with attenuated takes (P = .02) and reduced duration (P = .001) and titer (P = .005) of viral shedding., Conclusions: MVA immunization results in clinical and virologic protection against Dryvax challenge. Protection is associated with prior induction of neutralizing antibodies to MVA or vaccinia virus. MVA administered intradermally has protective and immunologic responses similar to those of a 10-fold-higher dose given subcutaneously.

Background: Diagnosis of invasive fungal disease (IFD) is challenging, and it remains a significant cause of morbidity and mortality in immunocompromised patients. The (1-->3)-beta-D-glucan (BG) assay may be a useful adjunct, but its diagnostic performance is not well characterized., Methods: We retrospectively assessed the diagnostic indices of the BG assay in patients at risk of IFD who had a compatible clinical syndrome for the diagnosis of IFD a week after initial BG testing and at the end of the hospitalization associated with the first BG value. Patients with IFD were classified according to current European Organization for Research and Treatment of Cancer-Mycoses Study Group criteria, independent of BG results., Results: A total of 1308 BG assays were performed for 871 patients. One hundred twelve proven or probable IFD cases were diagnosed within 1 week after initial testing, and 116 cases were diagnosed by the end of hospitalization. Sensitivity of an initial BG level 80 pg/mL for IFD at 1 week was 0.64 (95% confidence interval [CI], 0.55-0.73), specificity was 0.84 (95% CI, 0.81-0.86), the positive likelihood ratio was 3.93 (95% CI, 2.94-5.26), and the negative likelihood ratio was 0.43 (95% CI, 0.31-0.59). Albumin, intravenous immunoglobulin, and hemodialysis were associated with elevated BG levels in patients without IFD (odds ratio, 4.78; 95% CI, 2.59-8.80). After excluding patients with these factors, specificity and the positive likelihood ratio of an initial BG level 80 pg/mL increased slightly. Empirical systemic antifungal treatment did not reduce overall BG sensitivity. Sensitivity was slightly lower among patients with hematologic malignancy or stem cell transplantation. Consideration of BG results would have increased the diagnostic certainty to probable in 54% of possible IFD cases., Conclusions: BG level appears to be a fair diagnostic adjunct for IFD in patients with appropriate pretest probability and a suggestive clinical syndrome, especially when checked serially in patients not receiving factors associated with an elevated BG level in the absence of IFD.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Background: Alemtuzumab is an emerging therapy for refractory lymphoproliferative disorders. The associated long-term risks of infection remain poorly defined., Methods: From July 2001 through December 2003, all patients who received alemtuzumab for the treatment of lymphoproliferative disorders at 1 institution underwent a retrospective evaluation to document infectious complications until death or end of follow-up in October 2004. Alemtuzumab recipients who underwent allogeneic hematopoietic stem cell transplantation were compared with a concurrent cohort who also underwent allogeneic hematopoietic stem cell transplantation but did not receive alemtuzumab., Results: Twenty-seven patients were identified (21 with chronic lymphocytic leukemia and 6 with plasma cell disorders). The overall mortality was 37%, with 7 of 10 deaths being related to infection. Significant opportunistic infections occurred in 9 patients (43%) with chronic lymphocytic leukemia, including cytomegalovirus, progressive multifocal leukoencephalopathy, adenovirus, toxoplasmosis, and acanthamaebiasis. Thirty nonopportunistic infections in 22 patients (82%) were also identified. The 3 deaths related to nonopportunistic infections all involved Enterococcus species bacteremia. When compared with a concurrent chronic lymphocytic leukemia cohort that underwent allogeneic hematopoietic stem cell transplantation, alemtuzumab recipients had an incidence of cytomegalovirus reactivation of 66.7% (6 of 9 patients), compared with 37% in the non-alemtuzumab group (10 of 27 patients; P = .15), and an incidence of post-transplant opportunistic infections (excluding herpesviruses) of 44.4% (compared with 29.6% in the non-alemtuzumab group; P = .41)., Conclusions: Despite the use of herpesvirus and Pneumocystis pneumonia prophylaxis, serious infectious complications occur in patients receiving alemtuzumab for lymphoproliferative disorders. Infectious complications are more varied and diverse in patients receiving alemtuzumab than has been reported in trials to date.

Background: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants)., Results: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001)., Conclusions: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.

There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

Sputum induction for the diagnosis of Pneumocystis pneumonia (PCP) is widely used for patients with acquired immunodeficiency syndrome (AIDS), but its utility for patients with other forms of immunocompromise is less well defined. Immunocompromised patients with PCP who do not have human immunodeficiency virus (HIV) infection have a lower burden of organisms, and sputum induction may consequently have lower diagnostic yield in these patients. However, this retrospective review of the experience at a tertiary referral center suggests that sputum induction has clinical utility for diagnosing PCP in immunocompromised patients without HIV infection.