Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials

ABSTRACT A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected...

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Autores principales:	Eliza D. Hompe, Jesse F. Mangold, Amit Kumar, Joshua A. Eudailey, Erin McGuire, Barton F. Haynes, M. Anthony Moody, Peter F. Wright, Genevieve G. Fouda, Elena E. Giorgi, Feng Gao, Sallie R. Permar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV envelope autologous virus neutralization human immunodeficiency virus maternal vaccination mother-to-child transmission Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8f3973ffb24a434595bd4de143e970da
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spelling	oai:doaj.org-article:8f3973ffb24a434595bd4de143e970da2021-11-15T15:30:15ZInduction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials10.1128/mSphere.00254-202379-5042https://doaj.org/article/8f3973ffb24a434595bd4de143e970da2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00254-20https://doaj.org/toc/2379-5042ABSTRACT A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no. NCT00001041). Maternal HIV Env-specific plasma binding and neutralizing antibody responses were characterized before and after vaccination in 15 AVEG 104 (n = 10 vaccine recipients, n = 5 placebo recipients) and 2 AVEG 102 (n = 1 vaccine recipient, n = 1 placebo recipient) participants. Single-genome amplification (SGA) was used to obtain HIV env gene sequences of autologous maternal viruses for pseudovirus production and neutralization sensitivity testing in pre- and postvaccination plasma of HIV-infected pregnant vaccine recipients (n = 6 gp120, n = 1 gp160) and placebo recipients (n = 3). We detected an increase in Env subunit MN gp120-specific IgG binding in the group of vaccine recipients between the first immunization visit and the last visit at delivery (P = 0.027, 2-sided Wilcoxon test). While no difference was observed in the levels of autologous virus neutralization potency between groups, in both groups maternal plasma collected at delivery more effectively neutralized autologous viruses from early pregnancy than late pregnancy. Immunization strategies capable of further enhancing these autologous virus NAb responses in pregnant women will be important to block vertical transmission of HIV. IMPORTANCE Maternal antiretroviral therapy (ART) has effectively reduced but not eliminated the burden of mother-to-child transmission of HIV across the globe, as an estimated 160,000 children were newly infected with HIV in 2018. Thus, additional preventive strategies beyond ART will be required to close the remaining gap and end the pediatric HIV epidemic. A maternal active immunization strategy that synergizes with maternal ART could further reduce infant HIV infections. In this study, we found that two historic HIV Env vaccines did not enhance the ability of HIV-infected pregnant women to neutralize autologous viruses. Therefore, next-generation maternal HIV vaccine candidates must employ alternate approaches to achieve potent neutralizing antibody and perhaps nonneutralizing antibody responses to effectively impede vertical virus transmission. Moreover, these approaches must reflect the broad diversity of HIV strains and widespread availability of ART worldwide.Eliza D. HompeJesse F. MangoldAmit KumarJoshua A. EudaileyErin McGuireBarton F. HaynesM. Anthony MoodyPeter F. WrightGenevieve G. FoudaElena E. GiorgiFeng GaoSallie R. PermarAmerican Society for MicrobiologyarticleHIV envelopeautologous virus neutralizationhuman immunodeficiency virusmaternal vaccinationmother-to-child transmissionMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV envelope autologous virus neutralization human immunodeficiency virus maternal vaccination mother-to-child transmission Microbiology QR1-502
spellingShingle	HIV envelope autologous virus neutralization human immunodeficiency virus maternal vaccination mother-to-child transmission Microbiology QR1-502 Eliza D. Hompe Jesse F. Mangold Amit Kumar Joshua A. Eudailey Erin McGuire Barton F. Haynes M. Anthony Moody Peter F. Wright Genevieve G. Fouda Elena E. Giorgi Feng Gao Sallie R. Permar Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
description	ABSTRACT A maternal vaccine capable of boosting neutralizing antibody (NAb) responses directed against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women could enhance autologous virus neutralization and thereby reduce this risk of vertical HIV transmission. Here, we assessed autologous virus NAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) protocols 104 and 102, representing historical phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines administered to HIV-infected pregnant women (ClinicalTrials registration no. NCT00001041). Maternal HIV Env-specific plasma binding and neutralizing antibody responses were characterized before and after vaccination in 15 AVEG 104 (n = 10 vaccine recipients, n = 5 placebo recipients) and 2 AVEG 102 (n = 1 vaccine recipient, n = 1 placebo recipient) participants. Single-genome amplification (SGA) was used to obtain HIV env gene sequences of autologous maternal viruses for pseudovirus production and neutralization sensitivity testing in pre- and postvaccination plasma of HIV-infected pregnant vaccine recipients (n = 6 gp120, n = 1 gp160) and placebo recipients (n = 3). We detected an increase in Env subunit MN gp120-specific IgG binding in the group of vaccine recipients between the first immunization visit and the last visit at delivery (P = 0.027, 2-sided Wilcoxon test). While no difference was observed in the levels of autologous virus neutralization potency between groups, in both groups maternal plasma collected at delivery more effectively neutralized autologous viruses from early pregnancy than late pregnancy. Immunization strategies capable of further enhancing these autologous virus NAb responses in pregnant women will be important to block vertical transmission of HIV. IMPORTANCE Maternal antiretroviral therapy (ART) has effectively reduced but not eliminated the burden of mother-to-child transmission of HIV across the globe, as an estimated 160,000 children were newly infected with HIV in 2018. Thus, additional preventive strategies beyond ART will be required to close the remaining gap and end the pediatric HIV epidemic. A maternal active immunization strategy that synergizes with maternal ART could further reduce infant HIV infections. In this study, we found that two historic HIV Env vaccines did not enhance the ability of HIV-infected pregnant women to neutralize autologous viruses. Therefore, next-generation maternal HIV vaccine candidates must employ alternate approaches to achieve potent neutralizing antibody and perhaps nonneutralizing antibody responses to effectively impede vertical virus transmission. Moreover, these approaches must reflect the broad diversity of HIV strains and widespread availability of ART worldwide.
format	article
author	Eliza D. Hompe Jesse F. Mangold Amit Kumar Joshua A. Eudailey Erin McGuire Barton F. Haynes M. Anthony Moody Peter F. Wright Genevieve G. Fouda Elena E. Giorgi Feng Gao Sallie R. Permar
author_facet	Eliza D. Hompe Jesse F. Mangold Amit Kumar Joshua A. Eudailey Erin McGuire Barton F. Haynes M. Anthony Moody Peter F. Wright Genevieve G. Fouda Elena E. Giorgi Feng Gao Sallie R. Permar
author_sort	Eliza D. Hompe
title	Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
title_short	Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
title_full	Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
title_fullStr	Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
title_full_unstemmed	Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials
title_sort	induction of neutralizing responses against autologous virus in maternal hiv vaccine trials
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/8f3973ffb24a434595bd4de143e970da
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Induction of Neutralizing Responses against Autologous Virus in Maternal HIV Vaccine Trials

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