Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants

ABSTRACT Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal a...

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Autores principales:	David R. Martinez, Joshua J. Tu, Amit Kumar, Jesse F. Mangold, Riley J. Mangan, Ria Goswami, Elena E. Giorgi, Juilin Chen, Michael Mengual, Ayooluwa O. Douglas, Holly Heimsath, Kevin O. Saunders, Nathan I. Nicely, Joshua Eudailey, Giovanna Hernandez, Papa Kwadwo Morgan-Asiedu, Kevin Wiehe, Barton F. Haynes, M. Anthony Moody, Celia LaBranche, David C. Montefiori, Feng Gao, Sallie R. Permar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	bNAbs infant-T/F virus mother-to-child transmission HIV neutralization MTCT Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/547a9acf953c4c8cac9d486936a9784c
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spelling	oai:doaj.org-article:547a9acf953c4c8cac9d486936a9784c2021-11-15T15:57:03ZMaternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants10.1128/mBio.00176-202150-7511https://doaj.org/article/547a9acf953c4c8cac9d486936a9784c2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00176-20https://doaj.org/toc/2150-7511ABSTRACT Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT. IMPORTANCE Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.David R. MartinezJoshua J. TuAmit KumarJesse F. MangoldRiley J. ManganRia GoswamiElena E. GiorgiJuilin ChenMichael MengualAyooluwa O. DouglasHolly HeimsathKevin O. SaundersNathan I. NicelyJoshua EudaileyGiovanna HernandezPapa Kwadwo Morgan-AsieduKevin WieheBarton F. HaynesM. Anthony MoodyCelia LaBrancheDavid C. MontefioriFeng GaoSallie R. PermarAmerican Society for MicrobiologyarticlebNAbsinfant-T/F virusmother-to-child transmissionHIVneutralizationMTCTMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	bNAbs infant-T/F virus mother-to-child transmission HIV neutralization MTCT Microbiology QR1-502
spellingShingle	bNAbs infant-T/F virus mother-to-child transmission HIV neutralization MTCT Microbiology QR1-502 David R. Martinez Joshua J. Tu Amit Kumar Jesse F. Mangold Riley J. Mangan Ria Goswami Elena E. Giorgi Juilin Chen Michael Mengual Ayooluwa O. Douglas Holly Heimsath Kevin O. Saunders Nathan I. Nicely Joshua Eudailey Giovanna Hernandez Papa Kwadwo Morgan-Asiedu Kevin Wiehe Barton F. Haynes M. Anthony Moody Celia LaBranche David C. Montefiori Feng Gao Sallie R. Permar Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
description	ABSTRACT Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT. IMPORTANCE Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.
format	article
author	David R. Martinez Joshua J. Tu Amit Kumar Jesse F. Mangold Riley J. Mangan Ria Goswami Elena E. Giorgi Juilin Chen Michael Mengual Ayooluwa O. Douglas Holly Heimsath Kevin O. Saunders Nathan I. Nicely Joshua Eudailey Giovanna Hernandez Papa Kwadwo Morgan-Asiedu Kevin Wiehe Barton F. Haynes M. Anthony Moody Celia LaBranche David C. Montefiori Feng Gao Sallie R. Permar
author_facet	David R. Martinez Joshua J. Tu Amit Kumar Jesse F. Mangold Riley J. Mangan Ria Goswami Elena E. Giorgi Juilin Chen Michael Mengual Ayooluwa O. Douglas Holly Heimsath Kevin O. Saunders Nathan I. Nicely Joshua Eudailey Giovanna Hernandez Papa Kwadwo Morgan-Asiedu Kevin Wiehe Barton F. Haynes M. Anthony Moody Celia LaBranche David C. Montefiori Feng Gao Sallie R. Permar
author_sort	David R. Martinez
title	Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
title_short	Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
title_full	Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
title_fullStr	Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
title_full_unstemmed	Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants
title_sort	maternal broadly neutralizing antibodies can select for neutralization-resistant, infant-transmitted/founder hiv variants
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/547a9acf953c4c8cac9d486936a9784c
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Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants

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