Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques

ABSTRACT Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the pot...

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Autores principales:	Joshua A. Eudailey, Maria L. Dennis, Morgan E. Parker, Bonnie L. Phillips, Tori N. Huffman, Camden P. Bay, Michael G. Hudgens, Roger W. Wiseman, Justin J. Pollara, Genevieve G. Fouda, Guido Ferrari, David J. Pickup, Pamela A. Kozlowski, Koen K. A. Van Rompay, Kristina De Paris, Sallie R. Permar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	HIV-1 breast milk maternal vaccination oral challenge placental transfer transmission Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/24cdc256f1384177999d95017eb64e03
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spelling	oai:doaj.org-article:24cdc256f1384177999d95017eb64e032021-11-15T15:22:01ZMaternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques10.1128/mSphere.00505-172379-5042https://doaj.org/article/24cdc256f1384177999d95017eb64e032018-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00505-17https://doaj.org/toc/2379-5042ABSTRACT Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.Joshua A. EudaileyMaria L. DennisMorgan E. ParkerBonnie L. PhillipsTori N. HuffmanCamden P. BayMichael G. HudgensRoger W. WisemanJustin J. PollaraGenevieve G. FoudaGuido FerrariDavid J. PickupPamela A. KozlowskiKoen K. A. Van RompayKristina De ParisSallie R. PermarAmerican Society for MicrobiologyarticleHIV-1breast milkmaternal vaccinationoral challengeplacental transfertransmissionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 breast milk maternal vaccination oral challenge placental transfer transmission Microbiology QR1-502
spellingShingle	HIV-1 breast milk maternal vaccination oral challenge placental transfer transmission Microbiology QR1-502 Joshua A. Eudailey Maria L. Dennis Morgan E. Parker Bonnie L. Phillips Tori N. Huffman Camden P. Bay Michael G. Hudgens Roger W. Wiseman Justin J. Pollara Genevieve G. Fouda Guido Ferrari David J. Pickup Pamela A. Kozlowski Koen K. A. Van Rompay Kristina De Paris Sallie R. Permar Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
description	ABSTRACT Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.
format	article
author	Joshua A. Eudailey Maria L. Dennis Morgan E. Parker Bonnie L. Phillips Tori N. Huffman Camden P. Bay Michael G. Hudgens Roger W. Wiseman Justin J. Pollara Genevieve G. Fouda Guido Ferrari David J. Pickup Pamela A. Kozlowski Koen K. A. Van Rompay Kristina De Paris Sallie R. Permar
author_facet	Joshua A. Eudailey Maria L. Dennis Morgan E. Parker Bonnie L. Phillips Tori N. Huffman Camden P. Bay Michael G. Hudgens Roger W. Wiseman Justin J. Pollara Genevieve G. Fouda Guido Ferrari David J. Pickup Pamela A. Kozlowski Koen K. A. Van Rompay Kristina De Paris Sallie R. Permar
author_sort	Joshua A. Eudailey
title	Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
title_short	Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
title_full	Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
title_fullStr	Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
title_full_unstemmed	Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques
title_sort	maternal hiv-1 env vaccination for systemic and breast milk immunity to prevent oral shiv acquisition in infant macaques
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/24cdc256f1384177999d95017eb64e03
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Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques

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