852 results on '"Permar, Sallie R."'
Search Results
2. Novel Approaches to Postnatal Prophylaxis to Eliminate Vertical Transmission of HIV
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Ruel, Theodore, Penazzato, Martina, Zech, Jennifer M, Archary, Moherndran, Cressey, Tim R, Goga, Ameena, Harwell, Joseph, Landovitz, Raphael J, Lain, Maria Grazia, Lallemant, Marc, Namusoke-Magongo, Eleanor, Mukui, Irene, Permar, Sallie R, Prendergast, Andrew J, Shapiro, Roger, and Abrams, Elaine J
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Health Services and Systems ,Public Health ,Health Sciences ,Pediatric ,Infectious Diseases ,Pediatric AIDS ,Prevention ,HIV/AIDS ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Humans ,Infant ,Female ,HIV Infections ,Anti-HIV Agents ,Infectious Disease Transmission ,Vertical ,Breast Feeding ,Health services and systems ,Public health - Abstract
Despite progress in providing antiretroviral therapy to pregnant women living with HIV, a substantial number of vertical transmissions continue to occur. Novel approaches leveraging modern potent, safe, and well-tolerated antiretroviral drugs are urgently needed.
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- 2023
3. Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV
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Hansen, Scott G, Womack, Jennie L, Perez, Wilma, Schmidt, Kimberli A, Marshall, Emily, Iyer, Ravi F, Cleveland-Rubeor, Hillary, Otero, Claire E, Taher, Husam, Burgt, Nathan H Vande, Barfield, Richard, Randall, Kurt T, Morrow, David, Hughes, Colette M, Selseth, Andrea N, Gilbride, Roxanne M, Ford, Julia C, Caposio, Patrizia, Tarantal, Alice, Chan, Cliburn, Malouli, Daniel, Barry, Peter A, Permar, Sallie R, Picker, Louis J, and Frueh, Klaus
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Vaccine Related (AIDS) ,Genetics ,Vaccine Related ,Biotechnology ,Immunization ,Prevention ,Good Health and Well Being ,Animals ,Humans ,Cytomegalovirus ,Simian Immunodeficiency Virus ,Macaca mulatta ,Gene Expression ,Simian immunodeficiency virus ,AIDS vaccine ,AIDS/HIV ,T cells ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
Rhesus cytomegalovirus-based (RhCMV-based) vaccine vectors induce immune responses that protect ~60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction of effector memory-based (EM-biased) CD8+ T cells recognizing SIV peptides presented by major histocompatibility complex-E (MHC-E) instead of MHC-Ia. The phenotype, durability, and efficacy of RhCMV/SIV-elicited cellular immune responses were maintained when vector spread was severely reduced by deleting the antihost intrinsic immunity factor phosphoprotein 71 (pp71). Here, we examined the impact of an even more stringent attenuation strategy on vector-induced immune protection against SIV. Fusion of the FK506-binding protein (FKBP) degradation domain to Rh108, the orthologue of the essential human CMV (HCMV) late gene transcription factor UL79, generated RhCMV/SIV vectors that conditionally replicate only when the FK506 analog Shield-1 is present. Despite lacking in vivo dissemination and reduced innate and B cell responses to vaccination, Rh108-deficient 68-1 RhCMV/SIV vectors elicited high-frequency, durable, EM-biased, SIV-specific T cell responses in RhCMV-seropositive RMs at doses of ≥ 1 × 106 PFU. Strikingly, elicited CD8+ T cells exclusively targeted MHC-Ia-restricted epitopes and failed to protect against SIVmac239 challenge. Thus, Rh108-dependent late gene expression is required for both induction of MHC-E-restricted T cells and protection against SIV.
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- 2023
4. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge one year later
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Milligan, Emma C, Olstad, Katherine, Williams, Caitlin A, Mallory, Michael, Cano, Patricio, Cross, Kaitlyn A, Munt, Jennifer E, Garrido, Carolina, Lindesmith, Lisa, Watanabe, Jennifer, Usachenko, Jodie L, Hopkins, Lincoln, Immareddy, Ramya, Lakshmanappa, Yashavanth Shaan, Elizaldi, Sonny R, Roh, Jamin W, Sammak, Rebecca L, Pollard, Rachel E, Yee, JoAnn L, Herbek, Savannah, Scobey, Trevor, Miehlke, Dieter, Fouda, Genevieve, Ferrari, Guido, Gao, Hongmei, Shen, Xiaoying, Kozlowski, Pamela A, Montefiori, David, Hudgens, Michael G, Edwards, Darin K, Carfi, Andrea, Corbett, Kizzmekia S, Graham, Barney S, Fox, Christopher B, Tomai, Mark, Iyer, Smita S, Baric, Ralph, Reader, Rachel, Dittmer, Dirk P, Van Rompay, Koen KA, Permar, Sallie R, and De Paris, Kristina
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Immunization ,Emerging Infectious Diseases ,Infectious Diseases ,Prevention ,Biodefense ,Vaccine Related ,Pneumonia ,Pneumonia & Influenza ,Lung ,Biotechnology ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Animals ,Humans ,Infant ,SARS-CoV-2 ,COVID-19 Vaccines ,Macaca mulatta ,COVID-19 ,Viral Vaccines ,BNT162 Vaccine ,Antibodies ,Viral ,Antibodies ,Neutralizing ,Biological Sciences ,Medical and Health Sciences - Abstract
The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.
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- 2023
5. Cost‐effectiveness of broadly neutralizing antibody prophylaxis for HIV‐exposed infants in sub‐Saharan African settings
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Dugdale, Caitlin M, Ufio, Ogochukwu, Alba, Christopher, Permar, Sallie R, Stranix‐Chibanda, Lynda, Cunningham, Coleen K, Fouda, Genevieve G, Myer, Landon, Weinstein, Milton C, Leroy, Valériane, McFarland, Elizabeth J, Freedberg, Kenneth A, and Ciaranello, Andrea L
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Medical Microbiology ,Biomedical and Clinical Sciences ,Sexually Transmitted Infections ,Comparative Effectiveness Research ,Health Services ,Pediatric ,Prevention ,Pediatric AIDS ,HIV/AIDS ,Clinical Research ,Infectious Diseases ,Women's Health ,Cost Effectiveness Research ,Infection ,Good Health and Well Being ,Infant ,Newborn ,Humans ,Infant ,Female ,Child ,Pregnancy ,Broadly Neutralizing Antibodies ,HIV Infections ,Cost-Benefit Analysis ,Anti-Retroviral Agents ,HIV Antibodies ,Cote d'Ivoire ,Infectious Disease Transmission ,Vertical ,HIV-1 ,broadly neutralizing antibodies ,cost-effectiveness analysis ,HIV prevention and control ,infant HIV prophylaxis ,vertical HIV transmission ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionInfant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings.MethodsWe conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs.ResultsThe model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs.ConclusionsAt current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.
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- 2023
6. Mathematical Modeling of Rhesus Cytomegalovirus Transplacental Transmission in Seronegative Rhesus Macaques
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Gong, Yishu, Moström, Matilda, Otero, Claire, Valencia, Sarah, Tarantal, Alice F, Kaur, Amitinder, Permar, Sallie R, and Chan, Cliburn
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Microbiology ,Biological Sciences ,Brain Disorders ,Perinatal Period - Conditions Originating in Perinatal Period ,Pediatric ,Infectious Diseases ,Conditions Affecting the Embryonic and Fetal Periods ,Infant Mortality ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Humans ,Infant ,Animals ,Female ,Pregnancy ,Cytomegalovirus ,Macaca mulatta ,Placenta ,Cytomegalovirus Infections ,Disease Models ,Animal ,Infectious Disease Transmission ,Vertical ,Pregnancy Complications ,Infectious ,cytomegalovirus ,placental transmission ,rhesus macaques - Abstract
Approximately 0.7% of infants are born with congenital cytomegalovirus (CMV), making it the most common congenital infection. About 1 in 5 congenitally infected babies will suffer long-term sequelae, including sensorineural deafness, intellectual disability, and epilepsy. CMV infection is highly species-dependent, and the rhesus CMV (RhCMV) infection of rhesus monkey fetuses is the only animal model that replicates essential features of congenital CMV (cCMV) infection in humans, including placental transmission, fetal disease, and fetal loss. Using experimental data from RhCMV seronegative rhesus macaques inoculated with RhCMV in the late first to early second trimesters of pregnancy, we built and calibrated a mathematical model for the placental transmission of CMV. The model was then used to study the effect of the timing of inoculation, maternal immune suppression, and hyper-immune globulin infusion on the risk of placental transmission in the context of primary and reactivated chronic maternal CMV infection.
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- 2023
7. Assessing the impact of autologous virus neutralizing antibodies on viral rebound time in postnatally SHIV-infected ART-treated infant rhesus macaques
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Mainou, Ellie, Berendam, Stella J., Obregon-Perko, Veronica, Uffman, Emilie A., Phan, Caroline T., Shaw, George M., Bar, Katharine J., Kumar, Mithra R., Fray, Emily J., Siliciano, Janet M., Siliciano, Robert F., Silvestri, Guido, Permar, Sallie R., Fouda, Genevieve G., McCarthy, Janice, Chahroudi, Ann, Conway, Jessica M., and Chan, Cliburn
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- 2024
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8. Evaluating longitudinal cytomegalovirus-specific humoral immune responses and association with DNAemia risk in seropositive lung transplant recipients
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Harnois, Melissa J., Barfield, Richard, Dennis, Maria, Rodgers, Nicole, Pollara, Justin, Spies, Connor S., Snyder, Laurie D., Chan, Cliburn, Jackson, Annette M., Palmer, Scott M., and Permar, Sallie R.
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- 2024
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9. Frequent Development of Broadly Neutralizing Antibodies in Early Life in a Large Cohort of Children With Human Immunodeficiency Virus
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Lucier, Amanda, Fong, Youyi, Li, Shuk Hang, Dennis, Maria, Eudailey, Joshua, Nelson, Ashley, Saunders, Kevin, Cunningham, Coleen K, McFarland, Elizabeth, McKinney, Ross, Moody, M Anthony, LaBranche, Celia, Montefiori, David, Permar, Sallie R, and Fouda, Genevieve G
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Vaccine Related ,Prevention ,HIV/AIDS ,Infectious Diseases ,Vaccine Related (AIDS) ,Sexually Transmitted Infections ,Biotechnology ,Immunization ,Pediatric ,Infection ,Good Health and Well Being ,Adult ,Antibodies ,Neutralizing ,Broadly Neutralizing Antibodies ,Child ,Child ,Preschool ,Epitopes ,HIV Antibodies ,HIV Infections ,HIV-1 ,Humans ,Immunoglobulin G ,Infant ,antibodies ,broad neutralization ,pediatric HIV ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundRecent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults.MethodsWe evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.ResultsOne-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response.ConclusionsThese results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.
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- 2022
10. Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques
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Nettere, Danielle, Unnithan, Shakthi, Rodgers, Nicole, Nohara, Junsuke, Cray, Paul, Berry, Madison, Jones, Caroline, Armand, Lawrence, Li, Shuk Hang, Berendam, Stella J., Fouda, Genevieve G., Cain, Derek W., Spence, Taylor N., Granek, Joshua A., Davenport, Clemontina A., Edwards, Robert J., Wiehe, Kevin, Van Rompay, Koen K. A., Moody, M. Anthony, Permar, Sallie R., and Pollara, Justin
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- 2023
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11. Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection
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Valencia, Sarah M., Rochat, Eric, Harnois, Melissa J., Dennis, Maria, Webster, Helen S., Hora, Bhavna, Kumar, Amit, Wang, Hsuan-Yuan (Sherry), Li, Leike, Freed, Daniel, Zhang, Ningyan, An, Zhiqiang, Wang, Dai, and Permar, Sallie R.
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- 2023
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12. What are the key pediatric public policy priorities as the COVID-19 pandemic persists?
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Schleiss, Mark R., Permar, Sallie R., and John, Chandy C.
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- 2023
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13. Antibody attributes, Fc receptor expression, gestation and maternal SARS-CoV-2 infection modulate HSV IgG placental transfer
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Mahant, Aakash Mahant, Trejo, Fatima Estrada, Aguilan, Jennifer T., Sidoli, Simone, Permar, Sallie R., and Herold, Betsy C.
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- 2023
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14. Evolution of ocular defects in infant macaques following in utero zika virus infection
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Yiu, Glenn, Thomasy, Sara M, Casanova, M Isabel, Rusakevich, Alexander M, Keesler, Rebekah I, Watanabe, Jennifer, Usachenko, Jodie, Singapuri, Anil, Ball, Erin E, Bliss-Moreau, Eliza, Guo, Wendi, Webster, Helen, Singh, Tulika, Permar, Sallie R, Ardeshir, Amir, Coffey, Lark L, and Van Rompay, Koen KA
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Perinatal Period - Conditions Originating in Perinatal Period ,Rare Diseases ,Eye Disease and Disorders of Vision ,Neurosciences ,Infectious Diseases ,Congenital Structural Anomalies ,Infant Mortality ,Pediatric ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Reproductive health and childbirth ,Good Health and Well Being ,Animals ,Blood-Retinal Barrier ,Female ,Macaca ,Macaca mulatta ,Pregnancy ,Pregnancy Complications ,Infectious ,Prenatal Exposure Delayed Effects ,Retina ,Retinal Degeneration ,Retinal Ganglion Cells ,Virus Replication ,Zika Virus ,Zika Virus Infection ,Immunology ,Neurodevelopment ,Ophthalmology ,Retinopathy ,Biomedical and clinical sciences ,Health sciences - Abstract
Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood-retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.
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- 2020
15. Does congenital cytomegalovirus infection contribute to the development of acute lymphoblastic leukemia in children?
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Toor, Rajbir K, Semmes, Eleanor C, Walsh, Kyle M, Permar, Sallie R, and Giulino-Roth, Lisa
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- 2023
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16. Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission
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Cruz, Diana Vera, Nelson, Cody S, Tran, Dollnovan, Barry, Peter A, Kaur, Amitinder, Koelle, Katia, and Permar, Sallie R
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Biological Sciences ,Biotechnology ,Perinatal Period - Conditions Originating in Perinatal Period ,Pediatric ,Conditions Affecting the Embryonic and Fetal Periods ,Infectious Diseases ,2.1 Biological and endogenous factors ,2.2 Factors relating to the physical environment ,Aetiology ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Animals ,Antibodies ,Viral ,Cytomegalovirus ,Cytomegalovirus Infections ,Female ,Infectious Disease Transmission ,Vertical ,Macaca mulatta ,Pregnancy ,Pregnancy Complications ,Infectious ,Microbiology ,Immunology ,Medical Microbiology ,Virology ,Medical microbiology - Abstract
Human cytomegalovirus (HCMV) infection is the leading non-genetic cause of congenital birth defects worldwide. While several studies have addressed the genetic composition of viral populations in newborns diagnosed with HCMV, little is known regarding mother-to-child viral transmission dynamics and how therapeutic interventions may impact within-host viral populations. Here, we investigate how preexisting CMV-specific antibodies shape the maternal viral population and intrauterine virus transmission. Specifically, we characterize the genetic composition of CMV populations in a monkey model of congenital CMV infection to examine the effects of passively-infused hyperimmune globulin (HIG) on viral population genetics in both maternal and fetal compartments. In this study, 11 seronegative, pregnant monkeys were challenged with rhesus CMV (RhCMV), including a group pretreated with a standard potency HIG preparation (n = 3), a group pretreated with a high-neutralizing potency HIG preparation (n = 3), and an untreated control group (n = 5). Targeted amplicon deep sequencing of RhCMV glycoprotein B and L genes revealed that one of the three strains present in the viral inoculum (UCD52) dominated maternal and fetal viral populations. We identified minor haplotypes of this strain and characterized their dynamics. Many of the identified haplotypes were consistently detected at multiple timepoints within sampled maternal tissues, as well as across tissue compartments, indicating haplotype persistence over time and transmission between maternal compartments. However, haplotype numbers and diversity levels were not appreciably different between control, standard-potency, and high-potency pretreatment groups. We found that while the presence of maternal antibodies reduced viral load and congenital infection, it had no apparent impact on intrahost viral genetic diversity at the investigated loci. Interestingly, some minor haplotypes present in fetal and maternal-fetal interface tissues were also identified as minor haplotypes in corresponding maternal tissues, providing evidence for a loose RhCMV mother-to-fetus transmission bottleneck even in the presence of preexisting antibodies.
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- 2020
17. DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes
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Van Rompay, Koen KA, Keesler, Rebekah I, Ardeshir, Amir, Watanabe, Jennifer, Usachenko, Jodie, Singapuri, Anil, Cruzen, Christina, Bliss-Moreau, Eliza, Murphy, Ashley M, Yee, JoAnn L, Webster, Helen, Dennis, Maria, Singh, Tulika, Heimsath, Holly, Lemos, Danilo, Stuart, Jackson, Morabito, Kaitlyn M, Foreman, Bryant M, Burgomaster, Katherine E, Noe, Amy T, Dowd, Kimberly A, Ball, Erin, Woolard, Kevin, Presicce, Pietro, Kallapur, Suhas G, Permar, Sallie R, Foulds, Kathryn E, Coffey, Lark L, Pierson, Theodore C, and Graham, Barney S
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Reproductive Medicine ,Medical Microbiology ,Biomedical and Clinical Sciences ,Pediatric Research Initiative ,Immunization ,Pediatric ,Infectious Diseases ,Conditions Affecting the Embryonic and Fetal Periods ,Biotechnology ,Vaccine Related ,Prevention ,Perinatal Period - Conditions Originating in Perinatal Period ,3.4 Vaccines ,Prevention of disease and conditions ,and promotion of well-being ,Reproductive health and childbirth ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,Female ,Macaca mulatta ,Pregnancy ,Pregnancy Complications ,Infectious ,Vaccination ,Vaccines ,DNA ,Viremia ,Zika Virus ,Zika Virus Infection ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - Abstract
Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.
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- 2019
18. A geographically-weighted cost-effectiveness analysis of newborn CMV screening
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Lantos, Paul M, primary, Gantt, Soren, additional, Janko, Mark, additional, Dionne, Francois, additional, Permar, Sallie R, additional, and Fowler, Karen, additional
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- 2024
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19. Comparative Analysis of Within-Host Dynamics of Acute Infection and Viral Rebound Dynamics in Postnatally SHIV-Infected ART-Treated Infant Rhesus Macaques
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Mainou, Ellie, primary, Berendam, Stella J, additional, Obregon-Perko, Veronica, additional, Uffman, Emilie A, additional, Phan, Caroline T, additional, Shaw, George M, additional, Bar, Katharine J, additional, Kumar, Mithra R, additional, Fray, Emily J, additional, Siliciano, Janet M, additional, Siliciano, Robert F, additional, Silvestri, Guido, additional, Permar, Sallie R, additional, Fouda, Genevieve G, additional, McCarthy, Janice, additional, Chahroudi, Ann, additional, Chan, Cliburn, additional, and Conway, Jessica M, additional
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- 2024
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20. Addition of interleukin-6 receptor blockade to carfilzomib-based desensitization in a highly sensitized nonhuman primate model
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Anwar, Imran J., Ezekian, Brian, DeLaura, Isabel, Manook, Miriam, Schroder, Paul, Yoon, Janghoon, Curfman, Verna, Branum, Evelyn, Messina, Julia, Harnois, Melissa, Permar, Sallie R., Farris, Alton B., Kwun, Jean, and Knechtle, Stuart J.
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- 2022
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21. Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1
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Nelson, Ashley N., Dennis, Maria, Mangold, Jesse F., Li, Katherine, Saha, Pooja T., Cronin, Kenneth, Cross, Kaitlyn A., Kumar, Amit, Mangan, Riley J., Shaw, George M., Bar, Katharine J., Haynes, Barton, Moody, Anthony M., Munir Alam, S., Pollara, Justin, Hudgens, Michael G., Van Rompay, Koen K. A., De Paris, Kristina, and Permar, Sallie R.
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- 2022
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22. E-cigarette and food flavoring diacetyl alters airway cell morphology, inflammatory and antiviral response, and susceptibility to SARS-CoV-2
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Langel, Stephanie N., Kelly, Francine L., Brass, David M., Nagler, Andrew E., Carmack, Dylan, Tu, Joshua J., Travieso, Tatianna, Goswami, Ria, Permar, Sallie R., Blasi, Maria, and Palmer, Scott M.
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- 2022
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23. Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine.
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Hu, Xintao, Karthigeyan, Krithika P, Herbek, Savannah, Valencia, Sarah M, Jenks, Jennifer A, Webster, Helen, Miller, Itzayana G, Connors, Megan, Pollara, Justin, Andy, Caroline, Gerber, Linda M, Walter, Emmanuel B, Edwards, Kathryn M, Bernstein, David I, Hou, Jacob, Koch, Matthew, Panther, Lori, Carfi, Andrea, Wu, Kai, and Permar, Sallie R
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ANTIBODY-dependent cell cytotoxicity ,CLINICAL trial registries ,ANTIBODY formation ,IMMUNOGLOBULIN G ,HUMAN cytomegalovirus - Abstract
Background MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure. Methods A messenger RNA (mRNA)–based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients. Results mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses. Conclusions Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine. Clinical Trials Registration NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59). [ABSTRACT FROM AUTHOR]
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- 2024
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24. Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice.
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Woodyear, Sarah, Chandler, Tawny L., Kawagishi, Takahiro, Lonergan, Tom M., Patel, Vanshika A., Williams, Caitlin A., Permar, Sallie R., Ding, Siyuan, and Caddy, Sarah L.
- Subjects
ROTAVIRUS diseases ,ROTAVIRUS vaccines ,VACCINE effectiveness ,VIRAL shedding ,ORAL vaccines - Abstract
The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
- Author
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Goswami, Ria, Russell, Veronica S., Tu, Joshua J., Thomas, Charlene, Hughes, Philip, Kelly, Francine, Langel, Stephanie N., Steppe, Justin, Palmer, Scott M., Haystead, Timothy, Blasi, Maria, and Permar, Sallie R.
- Published
- 2021
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26. Immunogenicity of Monovalent mRNA-1273 and BNT162b2 Vaccines in Children Less Than 5 Years of Age
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Dalapati, Trisha, primary, Williams, Caitlin A., additional, Giorgi, Elena E., additional, Hurst, Jillian H., additional, Herbek, Savannah, additional, Chen, Jui-Lin, additional, Kosman, Christina, additional, Rotta, Alexandre T., additional, Turner, Nicholas A., additional, Pulido, Natalie, additional, Aquino, Jhoanna N., additional, Pfeiffer, Trevor S., additional, Rodriguez, Javier, additional, Fouda, Genevieve G., additional, Permar, Sallie R., additional, and Kelly, Matthew S., additional
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- 2024
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27. Correction for Rasmussen et al., “Virology—the path forward”
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Rasmussen, Angela L., primary, Gronvall, Gigi K., additional, Lowen, Anice C., additional, Goodrum, Felicia, additional, Alwine, James, additional, Andersen, Kristian G., additional, Anthony, Simon J., additional, Baines, Joel, additional, Banerjee, Arinjay, additional, Broadbent, Andrew J., additional, Brooke, Christopher B., additional, Campos, Samuel K., additional, Caposio, Patrizia, additional, Casadevall, Arturo, additional, Chan, Gary C., additional, Cliffe, Anna R., additional, Collins-McMillen, Donna, additional, Connell, Nancy, additional, Damania, Blossom, additional, Daugherty, Matthew D., additional, Debbink, Kari, additional, Dermody, Terence S., additional, DiMaio, Daniel, additional, Duprex, W. Paul, additional, Emerman, Michael, additional, Galloway, Denise A., additional, Garry, Robert F., additional, Goldstein, Stephen A., additional, Greninger, Alexander L., additional, Hartman, Amy L., additional, Hogue, Brenda G., additional, Horner, Stacy M., additional, Hotez, Peter J., additional, Jung, Jae U., additional, Kamil, Jeremy P., additional, Karst, Stephanie M., additional, Laimins, Lou, additional, Lakdawala, Seema S., additional, Landais, Igor, additional, Letko, Michael, additional, Lindenbach, Brett, additional, Liu, Shan-Lu, additional, Luftig, Micah, additional, McFadden, Grant, additional, Mehle, Andrew, additional, Morrison, Juliet, additional, Moscona, Anne, additional, Mühlberger, Elke, additional, Munger, Joshua, additional, Münger, Karl, additional, Murphy, Eain, additional, Neufeldt, Christopher J., additional, Nikolich, Janko Z., additional, O'Connor, Christine M., additional, Pekosz, Andrew, additional, Permar, Sallie R., additional, Pfeiffer, Julie K., additional, Popescu, Saskia V., additional, Purdy, John G., additional, Racaniello, Vincent R., additional, Rice, Charles M., additional, Runstadler, Jonathan A., additional, Sapp, Martin J., additional, Scott, Rona S., additional, Smith, Gregory A., additional, Sorrell, Erin M., additional, Speranza, Emily, additional, Streblow, Daniel, additional, Tibbetts, Scott A., additional, Toth, Zsolt, additional, Van Doorslaer, Koenraad, additional, Weiss, Susan R., additional, White, Elizabeth A., additional, White, Timothy M., additional, Wobus, Christiane E., additional, Worobey, Michael, additional, Yamaoka, Satoko, additional, and Yurochko, Andrew, additional
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- 2024
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28. Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity
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Otero, Claire E., primary, Petkova, Sophia, additional, Ebermann, Martin, additional, Taher, Husam, additional, John, Nessy, additional, Hoffmann, Katja, additional, Davalos, Angel, additional, Mostrom, Matilda J, additional, Gilbride, Roxanne M, additional, Papen, Courtney, additional, Barber-Axthelm, Aaron, additional, Scheef, Elizabeth A., additional, Barfield, Richard, additional, Sprehe, Lesli M., additional, Kendall, Savannah, additional, Manuel, Tabitha D, additional, Vande Burgt, Nathan, additional, Chan, Cliburn, additional, Streblow, Daniel N., additional, Hansen, Scott G., additional, Denton, Michael, additional, Streblow, Zachary, additional, Kaur, Amitinder, additional, Permar, Sallie R, additional, Frueh, Klaus, additional, Hengel, Hartmut, additional, Malouli, Daniel, additional, and Kolb, Philipp, additional
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- 2024
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29. Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques
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Singh, Tulika, primary, Miller, Itzayana G., additional, Venkatayogi, Sravani, additional, Webster, Helen, additional, Heimsath, Holly J., additional, Eudailey, Josh A., additional, Dudley, Dawn M., additional, Kumar, Amit, additional, Mangan, Riley J., additional, Thein, Amelia, additional, Aliota, Matthew T., additional, Newman, Christina M., additional, Mohns, Mariel S., additional, Breitbach, Meghan E., additional, Berry, Madison, additional, Friedrich, Thomas C., additional, Wiehe, Kevin, additional, O'Connor, David H., additional, and Permar, Sallie R., additional
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- 2024
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30. Virology—the path forward
- Author
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Rasmussen, Angela L., primary, Gronvall, Gigi K., additional, Lowen, Anice C., additional, Goodrum, Felicia, additional, Alwine, James, additional, Andersen, Kristian G., additional, Anthony, Simon J., additional, Baines, Joel, additional, Banerjee, Arinjay, additional, Broadbent, Andrew J., additional, Brooke, Christopher B., additional, Campos, Samuel K., additional, Caposio, Patrizia, additional, Casadevall, Arturo, additional, Chan, Gary C., additional, Cliffe, Anna R., additional, Collins-McMillen, Donna, additional, Connell, Nancy, additional, Damania, Blossom, additional, Daugherty, Matthew D., additional, Debbink, Kari, additional, Dermody, Terence S., additional, DiMaio, Daniel, additional, Duprex, W. Paul, additional, Emerman, Michael, additional, Galloway, Denise A., additional, Garry, Robert F., additional, Goldstein, Stephen A., additional, Greninger, Alexander L., additional, Hartman, Amy L., additional, Hogue, Brenda G., additional, Horner, Stacy M., additional, Hotez, Peter J., additional, Jung, Jae U., additional, Kamil, Jeremy P., additional, Karst, Stephanie M., additional, Laimins, Lou, additional, Lakdawala, Seema S., additional, Landais, Igor, additional, Letko, Michael, additional, Lindenbach, Brett, additional, Liu, Shan-Lu, additional, Luftig, Micah, additional, McFadden, Grant, additional, Mehle, Andrew, additional, Morrison, Juliet, additional, Moscona, Anne, additional, Mühlberger, Elke, additional, Munger, Joshua, additional, Münger, Karl, additional, Murphy, Eain, additional, Neufeldt, Christopher J., additional, Nikolich, Janko Z., additional, O'Connor, Christine M., additional, Pekosz, Andrew, additional, Permar, Sallie R., additional, Pfeiffer, Julie K., additional, Popescu, Saskia V., additional, Purdy, John G., additional, Racaniello, Vincent R., additional, Rice, Charles M., additional, Runstadler, Jonathan A., additional, Sapp, Martin J., additional, Scott, Rona S., additional, Smith, Gregory A., additional, Sorrell, Erin M., additional, Speranza, Emily, additional, Streblow, Daniel, additional, Tibbetts, Scott A., additional, Toth, Zsolt, additional, Van Doorslaer, Koenraad, additional, Weiss, Susan R., additional, White, Elizabeth A., additional, White, Timothy M., additional, Wobus, Christiane E., additional, Worobey, Michael, additional, Yamaoka, Satoko, additional, and Yurochko, Andrew, additional
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- 2024
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31. Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection in fetuses
- Author
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Marichannegowda, Manukumar Honnayakanahalli, Mengual, Michael, Kumar, Amit, Giorgi, Elena E., Tu, Joshua J., Martinez, David R., Romero-Severson, Ethan O., Li, Xiaojun, Feng, Liping, Permar, Sallie R., and Gao, Feng
- Published
- 2021
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32. Rhesus monkeys for a nonhuman primate model of cytomegalovirus infections
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Itell, Hannah L, Kaur, Amitinder, Deere, Jesse D, Barry, Peter A, and Permar, Sallie R
- Subjects
Microbiology ,Biological Sciences ,Immunization ,Infectious Diseases ,Biotechnology ,Vaccine Related ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Animals ,Coinfection ,Cytomegalovirus ,Cytomegalovirus Infections ,Disease Models ,Animal ,Humans ,Macaca mulatta ,Medical Microbiology - Abstract
Human cytomegalovirus (HCMV) is the leading opportunistic viral infection in solid organ transplant patients and is the most common congenitally transmitted pathogen worldwide. Despite the significant burden of disease HCMV causes in immunosuppressed patients and infected newborns, there are no licensed preventative vaccines or effective immunotherapeutic treatments for HCMV, largely due to our incomplete understanding of the immune correlates of protection against HCMV infection and disease. Though CMV species-specificity imposes an additional challenge in defining a suitable animal model for HCMV, nonhuman primate (NHP) CMVs are the most genetically related to HCMV. In this review, we discuss the advantages and applicability of rhesus monkey models for studying HCMV infections and pathogenesis and ultimately informing vaccine development.
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- 2017
33. Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys
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Nelson, Cody S, Cruz, Diana Vera, Tran, Dollnovan, Bialas, Kristy M, Stamper, Lisa, Wu, Huali, Gilbert, Margaret, Blair, Robert, Alvarez, Xavier, Itell, Hannah, Chen, Meng, Deshpande, Ashlesha, Chiuppesi, Flavia, Wussow, Felix, Diamond, Don J, Vandergrift, Nathan, Walter, Mark R, Barry, Peter A, Cohen-Wolkowiez, Michael, Koelle, Katia, Kaur, Amitinder, and Permar, Sallie R
- Subjects
Infectious Diseases ,Prevention ,Immunization ,Perinatal Period - Conditions Originating in Perinatal Period ,Vaccine Related ,Pediatric ,Infection ,Good Health and Well Being ,Infectious disease ,Vaccines - Abstract
Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission in the setting of primary maternal infection and subsequent viremia, which is required for placental virus exposure. Pregnant, CD4+ T cell-depleted, rhesus CMV-seronegative (RhCMV-seronegative) rhesus monkeys were treated with either standardly produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV mixture. HIG passive infusion provided complete protection against fetal loss in both groups. The dose-optimized, RhCMV-neutralizing HIG additionally inhibited placental transmission of RhCMV and reduced viral replication and diversity. Our findings suggest that the presence of durable and potently neutralizing antibodies at the time of primary infection can prevent transmission of systemically replicating maternal RhCMV to the developing fetus, and therefore should be a primary target of vaccines to eliminate this neonatal infection.
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- 2017
34. Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.
- Author
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Nguyen, Sydney M, Antony, Kathleen M, Dudley, Dawn M, Kohn, Sarah, Simmons, Heather A, Wolfe, Bryce, Salamat, M Shahriar, Teixeira, Leandro BC, Wiepz, Gregory J, Thoong, Troy H, Aliota, Matthew T, Weiler, Andrea M, Barry, Gabrielle L, Weisgrau, Kim L, Vosler, Logan J, Mohns, Mariel S, Breitbach, Meghan E, Stewart, Laurel M, Rasheed, Mustafa N, Newman, Christina M, Graham, Michael E, Wieben, Oliver E, Turski, Patrick A, Johnson, Kevin M, Post, Jennifer, Hayes, Jennifer M, Schultz-Darken, Nancy, Schotzko, Michele L, Eudailey, Josh A, Permar, Sallie R, Rakasz, Eva G, Mohr, Emma L, Capuano, Saverio, Tarantal, Alice F, Osorio, Jorge E, O'Connor, Shelby L, Friedrich, Thomas C, O'Connor, David H, and Golos, Thaddeus G
- Subjects
Lung ,Decidua ,Spleen ,Amniotic Fluid ,Umbilical Cord ,Fetus ,Placenta ,Animals ,Macaca mulatta ,Humans ,Pregnancy Complications ,Infectious ,Viremia ,Disease Models ,Animal ,RNA ,Viral ,Fetal Development ,Pregnancy ,Female ,Infectious Disease Transmission ,Vertical ,Zika Virus ,Zika Virus Infection ,Disease Models ,Animal ,Infectious Disease Transmission ,Vertical ,Pregnancy Complications ,Infectious ,RNA ,Viral ,Virology ,Microbiology ,Immunology ,Medical Microbiology - Abstract
Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.
- Published
- 2017
35. Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.
- Author
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Fan, Qihua, Nelson, Cody S, Bialas, Kristy M, Chiuppesi, Flavia, Amos, Joshua, Gurley, Thaddeus C, Marshall, Dawn Jones, Eudailey, Joshua, Heimsath, Holly, Himes, Jonathon, Deshpande, Ashlesha, Walter, Mark R, Wussow, Felix, Diamond, Don J, Barry, Peter A, Moody, M Anthony, Kaur, Amitinder, and Permar, Sallie R
- Subjects
Animals ,Macaca mulatta ,Cytomegalovirus ,Pregnancy Complications ,Infectious ,Cytomegalovirus Infections ,Disease Models ,Animal ,Pregnancy ,Female ,Infectious Disease Transmission ,Vertical ,congenital cytomegalovirus ,nonhuman primates ,vaccine ,Pregnancy Complications ,Infectious ,Disease Models ,Animal ,Infectious Disease Transmission ,Vertical ,Biotechnology ,Pediatric ,Immunization ,Vaccine Related ,Prevention ,Perinatal Period - Conditions Originating in Perinatal Period ,Infectious Diseases ,2.1 Biological and endogenous factors ,Infection ,Immunology ,Microbiology - Abstract
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4+ T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4+ T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMV-reactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model.
- Published
- 2017
36. Advances in nanomaterial vaccine strategies to address infectious diseases impacting global health
- Author
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Fries, Chelsea N., Curvino, Elizabeth J., Chen, Jui-Lin, Permar, Sallie R., Fouda, Genevieve G., and Collier, Joel H.
- Published
- 2021
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37. Early Outcomes of a New NIH Program to Support Research in Residency
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Price Rapoza, Maria, McElvaine, Allison, Conroy, Molly B., Okuyemi, Kolawole, Rouphael, Nadine, Teach, Stephen J., Widlansky, Michael, Williams, Chris, and Permar, Sallie R.
- Published
- 2022
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38. Dose escalation study of bovine lactoferrin in preterm infants: getting the dose right
- Author
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Kaufman, David A., Berenz, Andrew, Itell, Hannah L., Conaway, Mark, Blackman, Amy, Nataro, James P., and Permar, Sallie R.
- Subjects
Children -- Diseases ,Lactoferrins -- Usage -- Health aspects ,Infants (Premature) -- Care and treatment ,Biological sciences - Abstract
Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, although neonatal studies have demonstrated variable results, in part due to the lack of pharmacokinetic data and differences in the products tested. We conducted a prospective, dose escalation (100, 200, and 300 mg*[kg.sup.-1]*day (-1)) safety study of bovine lactoferrin (Glanbia Nutritionals, USA) dissolved in sterile water (100 mg*mL (-1)) for 30 days in preterm infants with birth weight Key words: lactoferrin, preterm infants, safety, infection prevention. La lactoferrine en tant que complement nutritionnel enteral est apparue comme une nouvelle therapie preventive contre les infections graves chez les prematures, bien que les etudes neonatales aient demontre des resultats variables, en partie en raison du manque de donnees pharmacocinetiques et des differences entre les produits. Les auteurs ont mene une etude prospective, a doses croissantes (100, 200 et 300 mg[kg.sup.-1][jour.sup.-1]), sur l'innocuite de la lactoferrine bovine (Glanbia Nutritionals, E.-U.) dissoute dans de l'eau sterile (100 mg*[mL.sup.-1]) pendant 30 jours chez des prematures Mots-cles: lactoferrine, nourrissons prematures, innocuite, prevention des infections., Introduction Infections in extremely low birth weight (ELBW) infants remain a leading cause of mortality and neurodevelopmental impairment (Stoll et al. 2015; Cheong et al. 2020). One novel approach for [...]
- Published
- 2021
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39. Systemic and mucosal levels of lactoferrin in very low birth weight infants supplemented with bovine lactoferrin
- Author
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Itell, Hannah L., Berenz, Andrew, Mangan, Riley J., Permar, Sallie R., and Kaufman, David A.
- Subjects
Birth weight, Low -- Care and treatment ,Lactoferrins -- Usage -- Health aspects ,Infants (Premature) -- Care and treatment ,Biological sciences - Abstract
Lactoferrin supplementation may help prevent infections in preterm infants, but the efficacy has varied with different doses and products. We assessed the absorption and excretion of bovine lactoferrin (bLF) in 31 infants receiving 100, 200, or 300 mg*[kg.sup.-1]*[day.sup.-1] of enteral bLF for 30 days. bLF and human lactoferrin (hLF) in infant saliva, blood, urine, and stool, as well as expressed (EBM) or donor breast milk (DBM) that were collected (i) before the treatment was initiated, (ii) at study day 22, and (iii) one week after treatment cessation, were measured using ELISA. During treatment, bLF was absorbed from the gastrointestinal tract and detected in plasma, saliva, and urine, as well as excreted in stool. Levels of bLF in the saliva and stool began to decline within 12 h after dosing, and bLF was undetectable in all samples one week after treatment. The concentrations of hLF exceeded those of bLF across sample types and time-points. Infants receiving EBM demonstrated higher levels of hLF in the saliva and stool than those receiving DBM. Neither bLF nor hLF levels varied by patient characteristics, bLF dosage, or infection status. This is the first study demonstrating bLF absorption into the bloodstream and distribution to saliva and urine in preterm infants. Future studies should further explore LF pharmacokinetics because higher and more frequent dosing may improve the clinical benefit of LF supplementation. Key words: lactoferrin, preterm infants, bovine, supplementation, postnatal infection. La supplementation en lactoferrine peut aider a prevenir les infections chez les prematures, mais son efficacite varie en fonction du dosage et des produits. Les auteurs ont evalue l'absorption et l'excretion de la lactoferrine bovine (bLF) chez trente et un nourrissons recevant 100, 200 ou 300 mg*[kg.sup.-1]*[jour.sup.-1] de bLF enterale pendant 30 jours. Les niveaux de bLF et de lactoferrine humaine (hLF) dans la salive, le sang, l'urine et les selles des nourrissons et dans le lait maternel exprime ou de donneuses (LME, LMD), preleves avant le debut du traitement, le 22e jour de l'etude et une semaine apres la fin du traitement ont ete mesures par ELISA. Pendant le traitement, la bLF etait absorbee par le tractus gastro-intestinal, detectee dans le plasma, la salive et l'urine, et excretee dans les selles. Les niveaux de bLF dans la salive et les selles commencaient a diminuer dans les 12 h suivant l'administration et la bLF etait indetectable dans tous les echantillons une semaine apres le traitement. Les concentrations de hLF depassaient celles de bLF dans tous les types d'echantillons et a tous les moments. Les nourrissons qui ont recu du LME presentaient des niveaux de hLF dans la salive et les selles plus eleves que les patients nourris au LMD. Ni les niveaux de bLF ni ceux de hLF ne variaient en fonction des caracteristiques du patient, de la dose de bLF ou du statut de l'infection. Il s'agit de la premiere etude qui demontre l'absorption de la bLF dans la circulation sanguine et sa distribution dans la salive et l'urine chez les prematures. Les etudes futures devraient explorer plus avant la pharmacocinetique de la LF, car un dosage plus eleve et plus frequent pourrait ameliorer le benefice clinique de la supplementation en LF. [Traduit par la Redaction] Mots-cles : lactoferrine, prematures, bovins, supplementation, infection postnatale., Introduction Lactoferrin (LF) supplementation has emerged as a strategy to prevent late-onset infections and associated complications in preterm, very low birth weight ( Although LF is found in high concentrations [...]
- Published
- 2021
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40. Cytomegalovirus as an immunomodulator across the lifespan
- Author
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Semmes, Eleanor C, Hurst, Jillian H, Walsh, Kyle M, and Permar, Sallie R
- Published
- 2020
- Full Text
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41. Immunogenicity of Monovalent mRNA-1273 and BNT162b2 Vaccines in Children <5 Years of Age.
- Author
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Dalapati, Trisha, Williams, Caitlin A., Giorgi, Elena E., Hurst, Jillian H., Herbek, Savannah, Jui-Lin Chen, Kosman, Christina, Rotta, Alexandre T., Turner, Nicholas A., Pulido, Natalie, Aquino, Jhoanna N., Pfeiffer, Trevor S., Rodriguez, Javier, Fouda, Genevieve G., Permar, Sallie R., and Kelly, Matthew S.
- Published
- 2024
- Full Text
- View/download PDF
42. Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques
- Author
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Jiang, Danting, primary, Goswami, Ria, additional, Dennis, Maria, additional, Heimsath, Holly, additional, Kozlowski, Pamela A., additional, Ardeshir, Amir, additional, Van Rompay, Koen K. A., additional, De Paris, Kristina, additional, Permar, Sallie R., additional, and Surana, Neeraj K., additional
- Published
- 2023
- Full Text
- View/download PDF
43. COVID-19 Research Delays Disproportionately Affected Pediatrician-Scientists from Backgrounds Under-Represented in Medicine
- Author
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Nelson, Adin, primary, Lam, Janet, additional, Permar, Sallie R., additional, and Abramson, Erika, additional
- Published
- 2023
- Full Text
- View/download PDF
44. Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.
- Author
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Nelson, Ashley N, primary, Shen, Xiaoying, additional, Venkatayogi, Sravani, additional, Zhang, Shiyu, additional, Ozorowski, Gabriel, additional, Dennis, Maria, additional, Sewall, Leigh M, additional, Milligan, Emma, additional, Davis, Dominique, additional, Cross, Kaitlyn, additional, Chen, Yue, additional, van Schooten, Jelle, additional, Eudaily, Joshua, additional, Isaac, John, additional, Memon, Saad, additional, Weinbaum, Carolyn, additional, Stanfield-Oakley, Sherry, additional, Byrd, Alliyah, additional, Chutkan, Suni, additional, Berendam, Stella, additional, Cronin, Kenneth, additional, Yasmeen, Anila, additional, Alam, S.Munir, additional, LeBranche, Celia, additional, Rogers, Kenneth, additional, Shirreff, Lisa, additional, Cupo, Albert, additional, Derking, Ronlad, additional, Villinger, Francois, additional, Klasse, Per Johan, additional, Ferrari, Guido, additional, Williams, Wilton B, additional, Hudgens, Michael G, additional, Ward, Andrew B, additional, Montefiori, David C, additional, VanRompay, Koen, additional, Wiehe, Kevin, additional, Moore, John P, additional, Sanders, Rogier W, additional, De Paris, Kristina, additional, and Permar, Sallie R, additional
- Published
- 2023
- Full Text
- View/download PDF
45. Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study
- Author
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Alba, Christopher, primary, Malhotra, Shelly, additional, Horsfall, Stephanie, additional, Barnhart, Matthew E., additional, Bekker, Adrie, additional, Chapman, Katerina, additional, Cunningham, Coleen K., additional, Fast, Patricia E., additional, Fouda, Genevieve G., additional, Freedberg, Kenneth A., additional, Goga, Ameena, additional, Ghazaryan, Lusine R., additional, Leroy, Valériane, additional, Mann, Carlyn, additional, McCluskey, Margaret M., additional, McFarland, Elizabeth J., additional, Muturi-Kioi, Vincent, additional, Permar, Sallie R., additional, Shapiro, Roger, additional, Sok, Devin, additional, Stranix-Chibanda, Lynda, additional, Weinstein, Milton C., additional, Ciaranello, Andrea L., additional, and Dugdale, Caitlin M., additional
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- 2023
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- View/download PDF
46. Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model
- Author
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Otero, Claire E., primary, Barfield, Richard, additional, Scheef, Elizabeth, additional, Nelson, Cody S., additional, Rodgers, Nicole, additional, Wang, Hsuan-Yuan, additional, Moström, Matilda J., additional, Manuel, Tabitha D., additional, Sass, Julian, additional, Schmidt, Kimberli, additional, Taher, Husam, additional, Papen, Courtney, additional, Sprehe, Lesli, additional, Kendall, Savannah, additional, Davalos, Angel, additional, Barry, Peter A., additional, Früh, Klaus, additional, Pollara, Justin, additional, Malouli, Daniel, additional, Chan, Cliburn, additional, Kaur, Amitinder, additional, and Permar, Sallie R., additional
- Published
- 2023
- Full Text
- View/download PDF
47. A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.
- Author
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Dankwa, Sedem, primary, Kosman, Christina, additional, Dennis, Maria, additional, Giorgi, Elena E., additional, Vuong, Kenneth, additional, Pahountis, Ioanna, additional, Garza, Ashley, additional, McCarthy, Janice, additional, Mayer, Bryan T., additional, Ngo, Julia T., additional, Enemuo, Chiamaka A., additional, Carnathan, Diane G., additional, Stanfield-Oakley, Sherry, additional, Berendam, Stella J., additional, Weinbaum, Carolyn, additional, Engelman, Kathleen, additional, Magnani, Diogo M., additional, Chan, Cliburn, additional, Ferrari, Guido, additional, Silvestri, Guido, additional, Amara, Rama R., additional, Chahroudi, Ann, additional, Permar, Sallie R., additional, Fouda, Genevieve G., additional, and Goswami, Ria, additional
- Published
- 2023
- Full Text
- View/download PDF
48. Protective effect of pre-existing natural immunity in a nonhuman primate reinfection model of congenital cytomegalovirus infection
- Author
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Moström, Matilda J., primary, Yu, Shan, additional, Tran, Dollnovan, additional, Saccoccio, Frances M., additional, Versoza, Cyril J., additional, Malouli, Daniel, additional, Mirza, Anne, additional, Valencia, Sarah, additional, Gilbert, Margaret, additional, Blair, Robert V., additional, Hansen, Scott, additional, Barry, Peter, additional, Früh, Klaus, additional, Jensen, Jeffrey D., additional, Pfeifer, Susanne P., additional, Kowalik, Timothy F., additional, Permar, Sallie R., additional, and Kaur, Amitinder, additional
- Published
- 2023
- Full Text
- View/download PDF
49. Protective mechanisms of nonneutralizing antiviral antibodies
- Author
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Chandler, Tawny L., primary, Yang, Agnes, additional, Otero, Claire E., additional, Permar, Sallie R., additional, and Caddy, Sarah L., additional
- Published
- 2023
- Full Text
- View/download PDF
50. Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission
- Author
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Bialas, Kristy M, Tanaka, Takayuki, Tran, Dollnovan, Varner, Valerie, Cisneros De La Rosa, Eduardo, Chiuppesi, Flavia, Wussow, Felix, Kattenhorn, Lisa, Macri, Sheila, Kunz, Erika L, Estroff, Judy A, Kirchherr, Jennifer, Yue, Yujuan, Fan, Qihua, Lauck, Michael, O'Connor, David H, Hall, Allison HS, Xavier, Alvarez, Diamond, Don J, Barry, Peter A, Kaur, Amitinder, and Permar, Sallie R
- Subjects
Conditions Affecting the Embryonic and Fetal Periods ,Pediatric ,Immunization ,Biotechnology ,Vaccine Related ,Prevention ,Perinatal Period - Conditions Originating in Perinatal Period ,Infectious Diseases ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Animals ,Antibodies ,Viral ,CD4-Positive T-Lymphocytes ,Cytomegalovirus Infections ,Disease Models ,Animal ,Female ,Infectious Disease Transmission ,Vertical ,Macaca mulatta ,Maternal-Fetal Exchange ,Pregnancy ,congenital cytomegalovirus ,rhesus model ,T-cell immunity ,neutralizing antibody ,rhesus CMV - Abstract
Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4(+) T-cell depleted at the time of inoculation. Animals that received the CD4(+) T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8(+) T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4(+) T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.
- Published
- 2015
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