510 results on '"Barouch DH"'
Search Results
2. Adenovirus vectors from various serotypes induce distinct cytokine profiles
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Teigler JE, Iampietro M, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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3. Development of a novel simian adenovirus 24 based vaccine vector
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Abbink P, Bradley RR, Ball F, Ng'ang'a D, Borducchi E, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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4. First-in-human phase 1 trial of the safety and immunogenicity of a recombinant adenovirus serotype 5 HVR48 (rAd5HVR48) HIV-1 vaccine
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Walsh SR, Seaman MS, Johnson JA, Tucker RP, Krause KH, Weijtens M, Pau MG, Goudsmit J, Dolin R, Barouch DH, and Baden LR
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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5. Full-length HIV-1 immunogens induce greater T lymphocyte responses to conserved epitopes than conserved-region-only HIV-1 immunogens in monkeys
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Stephenson KE, SanMiguel A, Simmons NL, Smith K, Szinger JJ, Korber BT, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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6. Evidence for Env-V2 sieve effect in breakthrough SIV MAC251 infections in rhesus monkeys vaccinated with Ad26/MVA and MVA/Ad26 constructs
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Sina S, Tovanabutra S, Sanders-Buell E, Bates A, Bose M, Howell S, Ibitamuno G, Lazzaro M, O'Sullivan A, Lee J, Cervenka T, Kuroiwa J, Baldwin K, Barouch DH, Robb M, O'Connell R, Michael NL, Kim JH, and Rolland M
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
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7. Gag-specific cellular immunity determines in vitro viral inhibition and in vivo virologic control following SIV challenges of vaccinated monkeys
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Stephenson KE, Li H, Walker BD, Michael NL, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
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8. Different memory T cell phenotypes are elicited by Ad5 and rare adenoviruses
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Penaloza P, Borducchi E, McNally A, Simmons N, Teigler J, Provine N, Tan W, Ahmed R, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
- View/download PDF
9. Accelerated heterologous prime-boost adenovirus vector-based SIV vaccine in neonatal rhesus monkeys
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Liu J, Li H, Iampietro M, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
- View/download PDF
10. Humoral immune response profiling with peptide microarrays
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Reimer U, Wenschuh H, Baden LR, Pau M, Weijtens M, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
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11. Adenovirus serotype 26 utilizes CD46 as primary cellular receptor and only transiently activates T lymphocytes following vaccination of rhesus monkeys
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Li H, Rhee EG, Masek-Hammerman K, Teigler JE, Abbink P, and Barouch DH
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
- View/download PDF
12. P17-13. Hexon hypervariable regions 4–7 contain important Ad5-specific neutralizing antibody epitopes
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Barouch DH, Maxfield LF, and Bradley RR
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
13. P17-22. Impact of rare adenovirus seroprevalence on HIV-1 acquisition in the Step study
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Barouch DH, Goudsmit J, McElrath MJ, Hural J, LaPorte A, Dilan R, Riggs AM, King SL, and Maxfield LF
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
14. P10-06. Adaptive immune responses elicited by recombinant adenovirus vectors exhibit partial MyD88 dependence
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Barouch DH, Kasturi SP, Pulendran B, and Rhee EG
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
15. P11-03. Mucosal trafficking and differentiation of vaccine-elicited CD8+ T-lymphocytes
- Author
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Barouch DH, Simmons NL, and Kaufman DR
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
16. Novel Adenovirus Vector-Based Vaccines for HIV
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Letvin N, Barouch DH, Havenga M, and Goudsmit J
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2005
- Full Text
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17. NS1 DNA vaccination protects against Zika infection through T cell-mediated immunity in immunocompetent mice.
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Grubor-Bauk, B, Wijesundara, DK, Masavuli, M, Abbink, P, Peterson, RL, Prow, NA, Larocca, RA, Mekonnen, ZA, Shrestha, A, Eyre, NS, Beard, MR, Gummow, J, Carr, J, Robertson, SA, Hayball, JD, Barouch, DH, and Gowans, EJ
- Abstract
The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.
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- 2019
18. HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound
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Offersen, R, Yu, W-H, Scully, EP, Julg, B, Euler, Z, Sadanand, S, Garcia-Dominguez, D, Zheng, L, Rasmussen, TA, Jennewein, MF, Linde, C, Sassic, J, Lofano, G, Vigano, S, Stephenson, KE, Fischinger, S, Suscovich, TJ, Lichterfeld, M, Lauffenburger, D, Rosenberg, ES, Allen, T, Altfeld, M, Charles, RC, Ostergaard, L, Tolstrup, M, Barouch, DH, Sogaard, OS, Alter, G, Offersen, R, Yu, W-H, Scully, EP, Julg, B, Euler, Z, Sadanand, S, Garcia-Dominguez, D, Zheng, L, Rasmussen, TA, Jennewein, MF, Linde, C, Sassic, J, Lofano, G, Vigano, S, Stephenson, KE, Fischinger, S, Suscovich, TJ, Lichterfeld, M, Lauffenburger, D, Rosenberg, ES, Allen, T, Altfeld, M, Charles, RC, Ostergaard, L, Tolstrup, M, Barouch, DH, Sogaard, OS, and Alter, G
- Abstract
Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.
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- 2020
19. International AIDS Society global scientific strategy: towards an HIV cure 2016
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Deeks, Sg, Lewin, Sr, Ross, Al, Ananworanich, J, Benkirane, M, Cannon, P, Chomont, N, Douek, D, Lifson, Jd, Lo, Yr, Kuritzkes, D, Margolis, D, Mellors, J, Persaud, D, Tucker, Jd, Barre-Sinoussi, F, International Aids Society Towards a Cure Working Group, International Aids Society Towards a Cure Working Group, Alter, G, Auerbach, J, Autran, B, Barouch, Dh, Behrens, G, Cavazzana, M, Chen, Z, Cohen, Ea, Corbelli, Gm, Eholié, S, Eyal, N, Fidier, S, Garcia, L, Grossman, C, Henderson, G, Henrich, Tj, Jefferys, R, Kiem, Hp, Mccune, J, Moodley, K, Newman, Pa, Nijhuis, M, Nsubuga, Ms, Ott, M, Palmer, S, Richman, D, Saez-Cirion, A, Sharp, M, Siliciano, J, Silvestri, G, Singh, J, Spire, B, Taylor, J, Tolstrup, M, Valente, S, van Lunzen, J, Walensky, R, Wilson, I, Zack, J, Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia, International and Scientific Relations Office, ANRS, Paris, France, Walter Reed Army Institute of Research, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), National Institutes of Health [Bethesda] (NIH), Frederick National Laboratory for Cancer Research (FNLCR), World Health Organization Regional Office for the Western Pacific, Manila, Philippines, Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Institut Pasteur [Paris] (IP), Ragon Institute of MGH, MIT and Harvard, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AIDS Institute, The University of Hong Kong, Pok Fu Lam, Hong Kong, Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), European AIDS Treatment Group, Italy, Programme PAC-CI, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire, Harvard School of Public Health, Imperial College London, The B-Change Group, Manila, Philippines, Treatment Action Group (TAG), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Stellenbosch University, Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada, University Medical Center [Utrecht], Joint Clinical Research Centre, University of California (UC), The Westmead Institute for Medical Research, University of California [San Diego] (UC San Diego), Independent HIV Education and Advocacy Consultant, San Francisco, California, USA, Emory University [Atlanta, GA], Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CARE Collaboratory Community Advisory Board, Palm Springs, California, USA., Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark., The Scripps Research Institute [La Jolla, San Diego], ViiV Healthcare, London, United Kingdom., Massachusetts General Hospital [Boston], Brown University School of Public Health, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Department of Medicine, Imperial College London, London, United Kingdom, University of California, Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Scripps Research Institute, Imperial College Healthcare NHS Trust- BRC Funding, American Foundation for AIDS Research, Medical Research Council (MRC), MRC DCS, British HIV Association (BHIVA), and Larose, Catherine
- Subjects
CD4(+) T-CELLS ,0301 basic medicine ,International Cooperation ,[SDV]Life Sciences [q-bio] ,VIRAL RESERVOIR ,Human immunodeficiency virus (HIV) ,Stakeholder engagement ,HIV Infections ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Research & Experimental Medicine ,medicine.disease_cause ,Medicine ,Societies, Medical ,IN-VIVO ,ComputingMilieux_MISCELLANEOUS ,HIGHLY PATHOGENIC SIV ,virus diseases ,LATENT HIV-1 ,11 Medical And Health Sciences ,General Medicine ,TREATMENT INTERRUPTION ,3. Good health ,[SDV] Life Sciences [q-bio] ,International AIDS Society Towards a Cure Working Group ,Medicine, Research & Experimental ,Goals ,Life Sciences & Biomedicine ,BROADLY NEUTRALIZING ANTIBODIES ,Biochemistry & Molecular Biology ,medicine.medical_specialty ,RALTEGRAVIR INTENSIFICATION ,Immunology ,education ,Article ,General Biochemistry, Genetics and Molecular Biology ,HISTONE DEACETYLASE INHIBITOR ,03 medical and health sciences ,Global population ,Acquired immunodeficiency syndrome (AIDS) ,SUPPRESSIVE ANTIRETROVIRAL THERAPY ,Journal Article ,Humans ,Organizational Objectives ,Acquired Immunodeficiency Syndrome ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,business.industry ,Research ,Cell Biology ,medicine.disease ,Antiretroviral therapy ,030104 developmental biology ,Treatment interruption ,Family medicine ,business - Abstract
Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.
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- 2016
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20. Inhibitory receptor expression on memory CD8 T cells following Ad vector immunization
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Penaloza-MacMaster, P, Alayo, QA, Ra, J, Provine, N, Larocca, R, Lee, B, and Barouch, DH
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viruses ,Genetic Vectors ,Programmed Cell Death 1 Receptor ,Public Health, Environmental and Occupational Health ,biochemical phenomena, metabolism, and nutrition ,CD8-Positive T-Lymphocytes ,veterinary(all) ,Article ,Adenoviridae ,Mice, Inbred C57BL ,Mice ,Infectious Diseases ,Immunology and Microbiology(all) ,PD-1 ,HIV-1 ,Molecular Medicine ,Animals ,Cytokines ,Adenovirus ,Female ,Immunization ,Vector ,Hepatitis A Virus Cellular Receptor 2 ,Immunologic Memory - Abstract
T cells are an important component of immune responses, and their function is influenced by their expression of inhibitory receptors. Immunization with alternative serotype adenovirus (Ad) vectors induces highly functional T cell responses with lower programmed cell death 1 (PD-1) expression and increased boostability relative to Ad5 vectors. However, a detailed phenotypic characterization of other inhibitory receptors is lacking, and it is unknown whether Ad5-induced CD8 T cells eventually recover function with time. In this report, we measure the expression of various inhibitory receptors and memory markers during early and late time points following vaccination with Ad5 and alternative serotype Ad vectors. CD8 T cells induced by Ad5 exhibited increased expression of the inhibitory receptor Tim-3 and showed decreased central memory differentiation as compared with alternative serotype Ad vectors, even a year following immunization. Moreover, relative to Ad5-primed mice, Ad26-primed mice exhibited substantially improved recall of SIV Gag-specific CD8 T cell responses following heterologous boosting with MVA or Ad35 vectors. We also demonstrate that low doses of Ad5 priming resulted in more boostable immune responses with lower PD-1 expression as compared to high Ad5 doses, suggesting a role for vector dose in influencing immune dysfunction following Ad5 vaccination. These data suggest that Ad5 vectors induce a long-term pattern of immune exhaustion that can be partly overcome by lowering vector dose and modulating inhibitory signals.
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- 2016
21. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination
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Trkola, A, Mahan, AE, Jennewein, MF, Suscovich, T, Dionne, K, Tedesco, J, Chung, AW, Streeck, H, Pau, M, Schuitemaker, H, Francis, D, Fast, P, Laufer, D, Walker, BD, Baden, L, Barouch, DH, Alter, G, Trkola, A, Mahan, AE, Jennewein, MF, Suscovich, T, Dionne, K, Tedesco, J, Chung, AW, Streeck, H, Pau, M, Schuitemaker, H, Francis, D, Fast, P, Laufer, D, Walker, BD, Baden, L, Barouch, DH, and Alter, G
- Abstract
Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo. .
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- 2016
22. Correction: Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.
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Mahan, AE, Jennewein, MF, Suscovich, T, Dionne, K, Tedesco, J, Chung, AW, Streeck, H, Pau, M, Schuitemaker, H, Francis, D, Fast, P, Laufer, D, Walker, BD, Baden, L, Barouch, DH, Alter, G, Mahan, AE, Jennewein, MF, Suscovich, T, Dionne, K, Tedesco, J, Chung, AW, Streeck, H, Pau, M, Schuitemaker, H, Francis, D, Fast, P, Laufer, D, Walker, BD, Baden, L, Barouch, DH, and Alter, G
- Abstract
[This corrects the article DOI: 10.1371/journal.ppat.1005456.].
- Published
- 2016
23. OA05-06 LB. First-in-human Phase 1 safety and immunigenicity of an adenovirus serotype 26 HIV-1 vaccine vector
- Author
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Baden, LR, primary, Dolin, R, additional, O'Brien, KL, additional, Abbink, P, additional, La Porte, A, additional, Seaman, MS, additional, Choi, E, additional, Tucker, R, additional, Weitjens, M, additional, Pau, MG, additional, Goudsmit, J, additional, and Barouch, DH, additional
- Published
- 2009
- Full Text
- View/download PDF
24. P17-22. Impact of rare adenovirus seroprevalence on HIV-1 acquisition in the Step study
- Author
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Maxfield, LF, primary, King, SL, additional, Riggs, AM, additional, Dilan, R, additional, LaPorte, A, additional, Hural, J, additional, McElrath, MJ, additional, Goudsmit, J, additional, and Barouch, DH, additional
- Published
- 2009
- Full Text
- View/download PDF
25. P17-13. Hexon hypervariable regions 4–7 contain important Ad5-specific neutralizing antibody epitopes
- Author
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Bradley, RR, primary, Maxfield, LF, additional, and Barouch, DH, additional
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- 2009
- Full Text
- View/download PDF
26. P11-03. Mucosal trafficking and differentiation of vaccine-elicited CD8+ T-lymphocytes
- Author
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Kaufman, DR, primary, Simmons, NL, additional, and Barouch, DH, additional
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- 2009
- Full Text
- View/download PDF
27. P10-06. Adaptive immune responses elicited by recombinant adenovirus vectors exhibit partial MyD88 dependence
- Author
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Rhee, EG, primary, Kasturi, SP, additional, Pulendran, B, additional, and Barouch, DH, additional
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- 2009
- Full Text
- View/download PDF
28. Novel Adenovirus Vector-Based Vaccines for HIV
- Author
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Barouch, DH, primary, Letvin, N, additional, Havenga, M, additional, and Goudsmit, J, additional
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- 2005
- Full Text
- View/download PDF
29. Novel immunological strategies for HIV-1 eradication
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Jülg, B and Barouch, DH
- Subjects
HIV-1 reservoir ,HIV-1 latency ,HIV-1 cure ,latency disruption ,therapeutic vaccines - Abstract
Despite the significant advances in antiretroviral therapy (ART), HIV-1 is able to persist in cellular reservoirs. Preclinical studies suggest that the latent reservoir is established within days of virus exposure, even before virus can be detected in peripheral blood. Latently infected cells remain undetectable by the immune system and can persist for years without losing their ability to produce infectious virus when ART is discontinued. Novel concepts for viral eradication strategies combine pharmacological induction of latently infected cells to produce virus together with immune-enhancing interventions to enable the host to clear these cells. In this review, we describe the early establishment of HIV-1 latency and discuss current strategies to disrupt latency and potentially enable clearance of these persistently infected cells.
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- 2015
30. P11-03. Mucosal Trafficking and Differentiation of Vaccine-Elicited CD8+ T-Lymphocytes
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Simmons, NL, Barouch, DH, and Kaufman, Diane Beth
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- 2009
- Full Text
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31. P10-06. Adaptive Immune Responses Elicited by Recombinant Adenovirus Vectors Exhibit Partial MyD88 Dependence
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Kasturi, SP, Pulendran, B, Barouch, DH, and Rhee, Edward
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- 2009
- Full Text
- View/download PDF
32. Accelerated Heterologous Prime-boost Adenovirus Vector-based SIV Vaccine in Neonatal Rhesus Monkeys
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Li, H, Barouch, DH, Iampietro, Mark Justin, and Liu, J.
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- 2012
- Full Text
- View/download PDF
33. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans
- Author
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Alter, G, primary, Yu, J, additional, Liu, J, additional, Chandrashekar, A, additional, Borducchi, EN, additional, Tostanoski, LT, additional, McMahan, K, additional, Jacob-Dolan, C, additional, Martinez, DR, additional, Chang, A, additional, Anioke, T, additional, Lifton, M, additional, Nkolola, J, additional, Stephenson, KE, additional, Atyeo, C, additional, Shin, S, additional, Fields, P, additional, Kaplan, I, additional, Robins, H, additional, Amanat, F, additional, Krammer, F, additional, Baric, RS, additional, Le Gars, M, additional, Sadoff, J, additional, de Groot, AM, additional, Heerwegh, D, additional, Struyf, F, additional, Douoguih, M, additional, van Hoof, J, additional, Schuitemaker, H, additional, and Barouch, DH, additional
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34. HIV escape from cytotoxic T lymphocytes: a potential hurdle for vaccines?
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Barouch DH and Letvin NL
- Published
- 2004
- Full Text
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35. NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice
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Rebecca Peterson, Zelalem A Mekonnen, Sarah A. Robertson, Jason Gummow, Jillian M. Carr, Natalie A. Prow, Dan H. Barouch, Michael R. Beard, Eric J. Gowans, Danushka K. Wijesundara, Peter Abbink, Branka Grubor-Bauk, John D. Hayball, Ashish C. Shrestha, Makutiro Ghislain Masavuli, Nicholas S. Eyre, Rafael A. Larocca, Grubor-Bauk, B, Wijesundara, DK, Masavuli, M, Abbink, P, Peterson, RL, Prow, NA, Larocca, RA, Mekonnen, ZA, Shrestha, A, Eyre, NS, Beard, MR, Gummow, J, Carr, J, Robertson, SA, Hayball, JD, Barouch, DH, and Gowans, EJ
- Subjects
Microcephaly ,Immunogen ,T cell ,viruses ,T-Lymphocytes ,Viral Nonstructural Proteins ,Guillain-Barre Syndrome ,Microbiology ,T cell mediated immunity ,Zika virus ,DNA vaccination ,03 medical and health sciences ,Epitopes ,Mice ,0302 clinical medicine ,Viral envelope ,Virology ,medicine ,Vaccines, DNA ,Animals ,Humans ,Research Articles ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,Zika Virus Infection ,virus diseases ,SciAdv r-articles ,DNA ,Zika Virus ,biology.organism_classification ,medicine.disease ,vaccination ,Disease Models, Animal ,medicine.anatomical_structure ,biology.protein ,Antibody ,030217 neurology & neurosurgery ,Research Article - Abstract
A novel T cell–based ZIKV vaccine, encoding NS1 protein, confers protection against systemic infection., The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell–based ZIKV vaccines.
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- 2019
36. COVID-19 vaccines: Immune correlates and clinical outcomes.
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Mahrokhian SH, Tostanoski LH, Vidal SJ, and Barouch DH
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- Humans, SARS-CoV-2, Antibodies, Neutralizing, Vaccination, Antibodies, Viral, COVID-19 Vaccines, COVID-19 prevention & control
- Abstract
Severe disease due to COVID-19 has declined dramatically as a result of widespread vaccination and natural immunity in the population. With the emergence of SARS-CoV-2 variants that largely escape vaccine-elicited neutralizing antibody responses, the efficacy of the original vaccines has waned and has required vaccine updating and boosting. Nevertheless, hospitalizations and deaths due to COVID-19 have remained low. In this review, we summarize current knowledge of immune responses that contribute to population immunity and the mechanisms how vaccines attenuate COVID-19 disease severity.
- Published
- 2024
- Full Text
- View/download PDF
37. Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques.
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Nkolola JP, Hope D, Guan R, Colarusso A, Aid M, Weiss D, Misamore J, Andersen H, Lewis MG, Williamson L, Carnahan RH, Crowe JE Jr, and Barouch DH
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- Animals, Humans, Mice, Female, Vero Cells, Neutralization Tests, Chlorocebus aethiops, Macaca mulatta, Zika Virus immunology, Zika Virus Infection immunology, Zika Virus Infection prevention & control, Zika Virus Infection virology, Antibodies, Neutralizing immunology, Antibodies, Monoclonal immunology, Antibodies, Viral immunology
- Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that caused a global pandemic in 2016-2017 with continued ongoing transmission at low levels in several countries. In the absence of an approved ZIKV vaccine, neutralizing monoclonal antibodies (mAbs) provide an option for the prevention and treatment of ZIKV infection. Previous studies identified a potent neutralizing human mAb ZIKV-117 that reduced fetal infection and death in mice following ZIKV challenge. In this study, we report exquisite potency of ZIKV-117-LALA-YTE, which has been engineered to reduce Fc receptor binding and to extend half-life, in a titration study in rhesus macaques to protect against ZIKV challenge. We show complete protection at a dose of 0.016 mg/kg ZIKV-117-LALA-YTE, which resulted in median serum concentrations of 0.13 µg/mL. The high potency of this mAb supports its potential clinical development as a novel biotherapeutic intervention for ZIKV.IMPORTANCEIn this study, we report the potency of the Zika virus (ZIKV)-specific neutralizing antibody ZIKV-117-LALA-YTE against ZIKV challenge in a titration study rhesus macaques. This high potency supports the further development of this monoclonal antibody for ZIKV., Competing Interests: J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, and Emergent Biosolutions; is a former member of the Scientific Advisory Boards of Gigagen (Grifols), Meissa Vaccines, and BTG International; is founder of IDBiologics; and receives royalties from UpToDate. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda Vaccines, and IDBiologics during the conduct of the study. All other authors declare no competing interests.
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- 2024
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38. Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.
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Edupuganti S, Hurt CB, Stephenson KE, Huang Y, Paez CA, Yu C, Yen C, Hanscom B, He Z, Miner MD, Gamble T, Heptinstall J, Seaton KE, Domin E, Lin BC, McKee K, Doria-Rose N, Regenold S, Spiegel H, Anderson M, McClosky N, Zhang L, Piwowar-Manning E, Ackerman ME, Pensiero M, Dye BJ, Landovitz RJ, Mayer K, Siegel M, Sobieszczyk M, Walsh SR, Gama L, Barouch DH, Montefiori DC, and Tomaras GD
- Abstract
Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults., Methods: In this first-in-human phase 1 trial (HVTN 136/HPTN 092), adults without HIV were enrolled at six university-affiliated clinical research sites in the USA. Part A evaluated escalating single intravenous doses or subcutaneous infusion of PGT121.414.LS, in four groups: 3 mg/kg intravenous (treatment group 1; n=3), 10 mg/kg intravenous (treatment group 2; n=4), 30 mg/kg intravenous (treatment group 3; n=3), and 5 mg/kg subcutaneous (treatment group 4; n=3). Part B evaluated repeated sequential intravenous administrations of 20 mg/kg PGT121.414.LS plus 20 mg/kg VRC07-523LS (treatment group 5; n=10) and sequential subcutaneous administrations of 5 mg/kg PGT121.414.LS plus 5 mg/kg VRC07-523LS (treatment group 6; n=10) on days 0, 112, and 224. Participants in treatment groups 1 and 2 were enrolled sequentially, with participants enrolled and randomly assigned to treatment groups 3 and 4 after a review of safety data. Participants in treatment groups 5 and 6 were randomly assigned in blocks after a review of safety data from treatment groups 1-4. The primary endpoints were safety and tolerability of mAbs, serum concentrations and pharmacokinetics of mAbs, and serum neutralising activity, assessed in participants who received all scheduled product administrations. Serum concentrations of each mAb were measured via a multiplex assay, and neutralisation activity against multiple HIV viruses was measured via the TZM-bl assay. Serum concentrations were estimated via an open, two-compartment model with first-order elimination from the central compartment. This study was registered with ClinicalTrials.gov (NCT04212091) and has been completed., Findings: Between Nov 10, 2020, and Oct 5, 2021, we enrolled 33 participants without HIV: median age was 31 years (range 22-48); 19 were assigned female sex at birth and 11 were assigned male sex at birth. Three participants and four participants were sequentially assigned to treatment groups 1 and 2, respectively, and, after safety review, six participants were randomly assigned to treatment groups 3 (n=3) and 4 (n=3); after safety review, 20 participants were randomly assigned to treatment groups 5 (n=10) and 6 (n=10). Intravenous and subcutaneous infusions were safe and well tolerated, without serious adverse events or dose-limiting toxicities. Dose escalation of PGT121.414.LS from 3 mg/kg to 30 mg/kg (intravenous) resulted in a dose-proportional increase in serum concentration of PGT121.414.LS, whether administered alone or in combination with VRC07-523LS. The estimated elimination half-life of PGT121.414.LS was 71 days (95% CI 66-75), three times that of its parental form, PGT121. The estimated subcutaneous (vs intravenous) bioavailability of PGT121.414.LS was 86·1% (95% CI 64·0-95·5). Neutralisation activities were greater in the higher-dose and dual combination intravenous groups than in the subcutaneous administration groups., Interpretation: These findings support further evaluation of PGT121.414.LS in combination with other mAbs for HIV-1 prevention., Funding: US National Institute of Allergy and Infectious Diseases and US National Institutes of Health., Competing Interests: Declaration of interests SRW has received institutional funding from the National Institute of Allergy and Infectious Diseases and US National Institutes of Health (NIH); institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; travel support from Sanofi; has participated on data safety monitoring or advisory boards for Janssen Vaccines (Johnson & Johnson) and BioNTech; and his spouse holds stock or stock options in Regeneron Pharmaceuticals. MEA reports grants to their institution from the Bill & Melinda Gates Foundation, Be Bio, and Moderna; royalties or licences from Elsevier; consulting fees from Seromyx Systems; and monies paid for travel and lectures or presentations from various academic centres and institutions. DHB is a co-inventor on the patent for PGT121.BIJ414.LS. JH, DCM, and KESe report reimbursement for travel from NIH. SE, CBH, MA, YH, JH, LZ, DCM, MP, KESe, and EP-M report grants from NIH. ND-R received funding for travel from CAPRISA. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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39. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.
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Julg B, Walker-Sperling VEK, Wagh K, Aid M, Stephenson KE, Zash R, Liu J, Nkolola JP, Hoyt A, Castro M, Serebryannyy L, Yanosick K, Speidel T, Borducchi EN, Murzda T, Maxfield L, Arduino R, McDermott AB, Gama L, Giorgi EE, Koup RA, Seaman MS, Rolle CP, DeJesus E, Li W, Korber B, and Barouch DH
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- Humans, Male, Adult, Female, Middle Aged, Broadly Neutralizing Antibodies immunology, Broadly Neutralizing Antibodies therapeutic use, CD4 Lymphocyte Count, Viral Load drug effects, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal immunology, HIV-1 immunology, HIV-1 drug effects, HIV Infections drug therapy, HIV Infections immunology, HIV Infections virology, HIV Antibodies immunology, Antibodies, Neutralizing immunology
- Abstract
Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies
1-4 . A combination of three bNAbs provides improved neutralization coverage of global viruses, which may more potently suppress viral escape and rebound5-7 . Here we performed an open-label, two-part study evaluating a single intravenous dose of HIV-1 bNAbs, PGT121, PGDM1400 and VRC07-523LS, in six adults without HIV in part 1 and a multicenter trial of up to six monthly infusions of these three bNAbs in 12 people living with HIV with an antiretroviral therapy (ART) interruption in part 2. The primary endpoints were safety, tolerability and pharmacokinetics, and the secondary endpoints in part 2 were antiviral activity following ART discontinuation, changes in CD4+ T cell counts and development of HIV-1 sequence mutations associated with bNAb resistance. The trial met its prespecified endpoints. The bNAb treatment was generally safe and well tolerated. In part 2, 83% of participants (10 of 12) maintained virologic suppression for the duration of antibody therapy for at least 28 weeks, and 42% of participants (5 of 12) showed virologic suppression for at least 38-44 weeks, despite the decline of serum bNAb concentrations to low or undetectable levels. In exploratory analyses, early viral rebound in two individuals correlated with baseline resistance to PGT121 and PGDM1400, whereas long-term virologic control in five individuals correlated with reduced immune activation, T cell exhaustion and proinflammatory signaling following bNAb therapy. Our data show the potential of a triple bNAb cocktail to suppress HIV-1 in the absence of ART. ClinicalTrials.gov registration: NCT03721510 ., Competing Interests: Competing interests: B.J. is a part-time employee of Leyden Labs, B.V. The other authors declare no competing interests., (© 2024. The Author(s).)- Published
- 2024
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40. Decline of Mpox Antibody Responses After Modified Vaccinia Ankara-Bavarian Nordic Vaccination.
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Collier AY, McMahan K, Jacob-Dolan C, Liu J, Borducchi EN, Moss B, and Barouch DH
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- 2024
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41. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial.
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Gray GE, Mngadi K, Lavreys L, Nijs S, Gilbert PB, Hural J, Hyrien O, Juraska M, Luedtke A, Mann P, McElrath MJ, Odhiambo JA, Stieh DJ, van Duijn J, Takalani AN, Willems W, Tapley A, Tomaras GD, Van Hoof J, Schuitemaker H, Swann E, Barouch DH, Kublin JG, Corey L, Pau MG, Buchbinder S, and Tomaka F
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- Humans, Female, Double-Blind Method, Adult, Young Adult, Adolescent, HIV Antibodies blood, Vaccine Efficacy, Africa, Southern, Adjuvants, Immunologic administration & dosage, HIV Infections prevention & control, AIDS Vaccines administration & dosage, AIDS Vaccines immunology, HIV-1 immunology
- Abstract
Background: HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa., Methods: This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18-35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7-24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov, NCT03060629, and is complete., Findings: Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20-25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7-24 after the first vaccination was 3·38 (95% CI 2·54-4·41) in the vaccine group and 3·94 (3·04-5·03) in the placebo group, with an estimated VE(7-24) of 14·10% (95% CI -22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE., Interpretation: The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1., Funding: Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute., Competing Interests: Declaration of interests GEG's institution (the South African Medical Research Council) has received funding from the US National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation. KM was a protocol co-chair for the Imbokodo trial. LL is a consultant for Janssen Infectious Diseases. SN, DJS, JvD, WW, JVH, HS, MGP, and FT were employees of Janssen Pharmaceuticals at the time of this study and are stockholders of Johnson & Johnson. AL's institution has received funding from the NIH; outside the submitted work, AL has received consulting fees from Harvard University, and his institution has received funding from Janssen Pharmaceuticals. PM is an employee and stockholder of CureVac. MJM's institution (Fred Hutchinson Cancer Center) has received funding, including for laboratory equipment purchases, from the HIV Vaccine Trials Network (HVTN) Laboratory Center (grant number 5UM1AI068618) and Seattle-Lausanne Clinical Trials Unit; outside the submitted work, her institution has received funding, including for laboratory equipment purchases, from the Scripps Consortium for HIV/AIDS Vaccine Development Subaward, National Institute of Allergy and Infectious Diseases (NIAID) Human Immunology Project Consortium 3, Bill & Melinda Gates Foundation Comprehensive Cellular Vaccine Immune Monitoring Consortium, and Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery; her institution has received funding, including for laboratory equipment purchases, supporting SARS-CoV-2 vaccine laboratory studies from the COVID-19 Prevention Network (NIAID), Janssen Pharmaceuticals, Infectious Diseases Clinical Research Consortium (NIAID), Sanofi Pasteur, Moderna, and Regeneron; her institution has received funding, including for laboratory equipment purchases, supporting HIV and other vaccine trials and laboratory studies from International AIDS Vaccine Initiative, Janssen Pharmaceuticals, and Vir Biotechnology; and she has participated in scientific advisory boards for the Ragon Institute and Keystone Symposia, and on a board of scientific counsellors for the NIH Vaccine Research Center. GDT's institution (Duke University) has received NIH funding through the HVTN (grant numbers 5UM1AI068614 and 5UM1AI068618); GDT has served as a consultant for and received funding to her institution through Janssen Pharmaceuticals; is a reviewer for the Gilead Research Scholar Program; and has served on the board of scientific counsellors for the NIH Vaccine Research Center. DHB is a co-inventor on HIV vaccine patents that have been licensed to Janssen Pharmaceuticals. SB has received grant funding from Gilead Sciences, Merck, GSK, and ViiV. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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42. Insights from an observational translational research program during the COVID-19 pandemic: Four years of experience.
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Rowe M, Collier AY, and Barouch DH
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- Humans, Female, Male, Adult, Middle Aged, Pregnancy, Boston epidemiology, Young Adult, Aged, Adolescent, Pandemics prevention & control, Vaccination, Immunization, Secondary, Child, Aged, 80 and over, COVID-19 prevention & control, COVID-19 epidemiology, COVID-19 immunology, Translational Research, Biomedical, SARS-CoV-2 immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage
- Abstract
The COVID-19 Biorepository at Beth Israel Deaconess Medical Center in Boston was initiated in 2020 to address questions about COVID-19 infection and vaccination in a time of urgent need. From April 2020 through July 2024, we enrolled 1018 participants and collected thousands of biospecimens. We enrolled participants from the general population as well as from specific populations that were not well represented in clinical trials, including immunosuppressed, pregnant, and lactating individuals. Our observational study was designed to accommodate the rapidly changing landscape of the pandemic, including the introduction of new vaccines and boosters, breakthrough infections, and emerging variants. Reflecting on the past four years of this experience, we believe that teamwork, collaboration, and flexibility were key factors for the success of this effort, which generated data in real time about COVID-19 vaccine responses in multiple populations, hybrid immunity following breakthrough infections, immune evasion of emerging variants, and immune imprinting following booster immunizations. Rapid dissemination of data through preprints, peer-reviewed publications, and public communications allowed for the real time use of our findings to address public health issues and to inform vaccine policies. The dedication of the study participants, clinical investigators, and laboratory investigators made this research program possible., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dan Barouch reports financial support was provided by Massachusetts Consortium on Pathogen Readiness. Dan Barouch, Ai-ris Collier reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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43. SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity.
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Lasrado N, Rowe M, McMahan K, Hachmann NP, Miller J, Jacob-Dolan C, Liu J, Verrette B, Gotthardt KA, Ty DM, Pereira J, Mazurek CR, Hoyt A, Collier AY, and Barouch DH
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- Humans, Female, Vaccination, Immunoglobulin A immunology, Immunoglobulin A blood, RNA, Messenger genetics, RNA, Messenger metabolism, Animals, Adult, Immunity, Mucosal immunology, SARS-CoV-2 immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Immunization, Secondary, Antibodies, Viral immunology, Antibodies, Viral blood, COVID-19 immunology, COVID-19 prevention & control, COVID-19 virology
- Abstract
Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections.
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- 2024
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44. Early spatiotemporal evolution of the immune response elicited by adenovirus serotype 26 vector vaccination in mice.
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Blass E, Colarusso A, Aid M, Larocca RA, Reeves RK, and Barouch DH
- Abstract
As the first responder to immunological challenges, the innate immune system shapes and regulates the ensuing adaptive immune response. Many clinical studies evaluating the role of innate immunity in initiating vaccine-elicited adaptive immune responses have largely been confined to blood due to inherent difficulty in acquiring tissue samples. However, the absence of vaccine-site and draining lymph node information limits understanding of early events induced by vaccination that could potentially shape vaccine-elicited immunity. We therefore utilized a mouse model to investigate the spatiotemporal evolution of the immune response within the first 24 hours following intramuscular adenovirus serotype 26 (Ad26) vector vaccination in tissues. We show that the Ad26 vaccine-elicited innate immune response commences by one hour and rapidly evolves in tissues and blood within the first 24 hours as reflected by the detection of cytokines, chemokines, cellular responses, and transcriptomic pathways. Furthermore, serum levels of IL-6, MIG, MIP-1α, and MIP-1β at 6 hours post-vaccination correlated with the frequency of vaccine-elicited memory CD8
+ T cell responses evaluated at 60 days post-vaccination in blood and tissues. Taken together, our data suggests that the immune response to Ad26 vector vaccination commences quickly in tissues by one hour and that events by as early as 6 hours post-vaccination can shape vaccine-elicited CD8+ T cell responses at later memory time points.- Published
- 2024
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45. Identification of a novel neutralization epitope in rhesus AAVs.
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Dagotto G, Fisher JL, Li D, Li Z, Jenni S, Li Z, Tartaglia LJ, Abbink P, and Barouch DH
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Adeno-associated viruses (AAVs) are popular gene therapy delivery vectors, but their application can be limited by anti-vector immunity. Both preexisting neutralizing antibodies (NAbs) and post-administration NAbs can limit transgene expression and reduce the clinical utility of AAVs. The development of novel AAVs will advance our understanding of AAV immunity and may also have practical applications. In this study, we identified five novel AAV capsids from rhesus macaques. RhAAV4282 exhibited 91.4% capsid sequence similarity with AAV7 and showed similar tissue tropism with slightly diminished overall signal. Despite this sequence homology, RhAAV4282 and AAV7 showed limited cross-neutralization. We determined a cryo-EM structure of the RhAAV4282 capsid at 2.57 Å resolution and identified a small segment within the hypervariable region IV, involving seven amino acids that formed a shortened external loop in RhAAV4282 compared with AAV7. We generated RhAAV4282 and AAV7 mutants that involved swaps of this region and showed that this region partially determined neutralization phenotype. We termed this region the hypervariable region IV neutralizing epitope (HRNE). Our data suggests that modification of the HRNE can lead to AAVs with altered neutralization profiles., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)
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- 2024
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46. Immune correlates analysis of the Imbokodo (HVTN 705/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study.
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Kenny A, van Duijn J, Dintwe O, Heptinstall J, Burnham R, Sawant S, Zhang L, Mielke D, Khuzwayo S, Omar FL, Stanfield-Oakley S, Keyes T, Dunn B, Goodman D, Fong Y, Benkeser D, Zou R, Hural J, Hyrien O, Juraska M, Luedtke A, van der Laan L, Giorgi EE, Magaret C, Carpp LN, Pattacini L, van de Kerkhof T, Korber B, Willems W, Fisher LH, Schuitemaker H, Swann E, Kublin JG, Pau MG, Buchbinder S, Tomaka F, Nijs S, Lavreys L, Gelderblom HC, Corey L, Mngadi K, Gray GE, Borducchi E, Hendriks J, Seaton KE, Zolla-Pazner S, Barouch DH, Ferrari G, De Rosa SC, McElrath MJ, Andersen-Nissen E, Stieh DJ, Tomaras GD, and Gilbert PB
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- Humans, Female, Case-Control Studies, Male, Adult, Vaccine Efficacy, HIV Antibodies blood, HIV Antibodies immunology, Immunoglobulin G blood, Immunoglobulin G immunology, env Gene Products, Human Immunodeficiency Virus immunology, Africa, Southern, Young Adult, Southern African People, AIDS Vaccines immunology, AIDS Vaccines administration & dosage, HIV Infections immunology, HIV Infections prevention & control, HIV Infections virology, HIV-1 immunology
- Abstract
Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: -22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models., Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case-control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions., Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: -17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: -17.9% to 89.6%), and further increased to 80.9% (95% CI: -17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker., Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen., Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV., Competing Interests: Declaration of interests TvdK has a patent application with Johnson & Johnson and has stocks in Johnson & Johnson. BK received internal support for the present manuscript from her employer (Los Alamos National Laboratory). In the past 36 months, she received support for attending meetings and/or travel from NIH NIAID and from the Gates foundation. Her institution (LANL) had a patent on this work, although she did not receive any personal funds through this patent and was not involved with the licensing of the design to Johnson & Johnson. DHB has a patent on the mosaic HIV vaccine, but no royalties. FT was an employee of Janssen/Johnson & Johnson at the time the work was conducted and owns stock in Johnson & Johnson. LL received support from Janssen Infectious Diseases BV, Beerse, Belgium for travel expenses to attend HIV conferences and has stock or stock options in Johnson & Johnson. JvD, MGP, WW, TvdK and JHen are employees of Janssen/Johnson & Johnson and hold stock or stock options in Johnson & Johnson. WW has a patent planned, issued, or pending with Johnson & Johnson. SCDR had contracts in the past 36 months to perform immunogenicity testing for Janssen, Sanofi, and Moderna. HS and DJS were employees of Janssen Vaccines & Prevention BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. SN was an employee of Janssen Infectious Diseases BV and had stock and/or stock options in Johnson & Johnson at the time the work was conducted. LP was an employee of Janssen Vaccines & Prevention BV at the time the work was conducted. GDT has received consulting fees for a scientific consulting session. All other authors have no potential competing interests to disclose. Funding for the Imbokodo Study and Correlates Group is the same as listed in “Acknowledgments” for the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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47. Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates.
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Vanshylla K, Tolboom J, Stephenson KE, Feddes-de Boer K, Verwilligen A, Rosendahl Huber SK, Rutten L, Schuitemaker H, Zahn RC, Barouch DH, and Wegmann F
- Abstract
The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
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48. High Frequency of Prior Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Sensitive Nucleocapsid Assays.
- Author
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Nkolola JP, Liu J, Collier AY, Jacob-Dolan C, Senussi Y, Borberg E, Swank Z, Walt DR, and Barouch DH
- Subjects
- Humans, Middle Aged, Antibodies, Viral blood, Female, Male, Nucleocapsid immunology, Adult, COVID-19 Serological Testing methods, Sensitivity and Specificity, Aged, Coronavirus Nucleocapsid Proteins immunology, T-Lymphocytes immunology, Cytokines blood, COVID-19 diagnosis, COVID-19 immunology, COVID-19 epidemiology, SARS-CoV-2 immunology
- Abstract
Prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is typically measured by nucleocapsid serology assays. In this study, we show that the Simoa serology assay and T-cell intracellular cytokine staining assay are more sensitive than the clinical Elecsys assay for detection of nucleocapsid-specific immune responses. These data suggest that the prevalence of prior SARS-CoV-2 infection in the population may be higher than currently appreciated., Competing Interests: Potential conflicts of interest. D. R. W. is an inventor of the Simoa technology and is a co-founder and serves on the board of directors of Quanterix Corporation. All other authors report no conflicts of interest. The 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.)
- Published
- 2024
- Full Text
- View/download PDF
49. Mpox infection of stromal cells and macrophages of macaque with endometriosis.
- Author
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Hall JM, Lyons CE, Li J, Martinez-Romero G, Hayes T, Cook A, Barouch DH, and Martinot AJ
- Subjects
- Animals, Female, Humans, Male, Endometriosis pathology, Endometriosis virology, Macaca mulatta, Macrophages virology, Macrophages metabolism, Stromal Cells pathology, Stromal Cells virology, Mpox (monkeypox) pathology
- Abstract
The mpox outbreak of 2022-2023 represented a new global health challenge and recognition of mpox as a sexually transmitted disease. The majority of cases were reported in men who have sex with men (MSM), but women are also susceptible, especially during pregnancy. We evaluated the reproductive tracts of a subset of macaques from a large rechallenge study of mpox infection with virus from the 2022 outbreak and identified intraabdominal mpox replication associated with endometriosis. Mpox virus (MPXV) was found not only in skin, but in the cervix, the uterus, and periovarian endometriotic lesions of the affected macaque. Mpox replication preferentially targeted vimentin-positive poorly differentiated endometriotic stromal tissue and infiltrating macrophages in the reproductive tract. Mpox tropism for stromal cells and macrophages has broad implications for mpox pathogenesis and associated clinical syndromes. In addition, women with endometriosis may be at heightened risk for adverse outcomes associated with mpox infection. The rhesus macaque provides rare insight into this disease and the potential complications of mpox infection in the context of genitourinary tract disease., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
50. Rapid Decline of Mpox Antibody Responses Following MVA-BN Vaccination.
- Author
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Collier AY, McMahan K, Jacob-Dolan C, Liu J, Borducchi EN, Moss B, and Barouch DH
- Abstract
The replication-incompetent modified vaccinia Ankara-Bavarian Nordic vaccine (MVA-BN; Jynneos) was deployed during the 2022 clade IIb mpox outbreak. On August 14, 2024, the World Health Organization declared the mpox clade Ib outbreak in the Democratic Republic of the Congo a public health emergency of international concern, which has raised the question about the durability of vaccine immunity after MVA-BN vaccination. In this study, we show that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6-12 months., Competing Interests: Conflicts of Interest The authors report no conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
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