Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity

ABSTRACT A significant number of infants acquire HIV-1 through their infected mother’s breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting result...

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Autores principales:	Melissa Ghulam-Smith, Alex Olson, Laura F. White, Charles S. Chasela, Sascha R. Ellington, Athena P. Kourtis, Denise J. Jamieson, Gerald Tegha, Charles M. van der Horst, Manish Sagar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	HIV MTCT antibodies breast milk infant mortality Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9a80cb0441ee479eb38999a0594d3b71
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spelling	oai:doaj.org-article:9a80cb0441ee479eb38999a0594d3b712021-11-15T15:51:51ZMaternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity10.1128/mBio.01373-172150-7511https://doaj.org/article/9a80cb0441ee479eb38999a0594d3b712017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01373-17https://doaj.org/toc/2150-7511ABSTRACT A significant number of infants acquire HIV-1 through their infected mother’s breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n = 63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n = 42), compared to those that eventually acquired infection (n = 21), did not possess higher nAb responses against heterologous envelopes (P = 0.46) or their mothers’ variants (P = 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P = 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P = 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P = 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity. IMPORTANCE Passive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby.Melissa Ghulam-SmithAlex OlsonLaura F. WhiteCharles S. ChaselaSascha R. EllingtonAthena P. KourtisDenise J. JamiesonGerald TeghaCharles M. van der HorstManish SagarAmerican Society for MicrobiologyarticleHIVMTCTantibodiesbreast milkinfant mortalityMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV MTCT antibodies breast milk infant mortality Microbiology QR1-502
spellingShingle	HIV MTCT antibodies breast milk infant mortality Microbiology QR1-502 Melissa Ghulam-Smith Alex Olson Laura F. White Charles S. Chasela Sascha R. Ellington Athena P. Kourtis Denise J. Jamieson Gerald Tegha Charles M. van der Horst Manish Sagar Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
description	ABSTRACT A significant number of infants acquire HIV-1 through their infected mother’s breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n = 63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n = 42), compared to those that eventually acquired infection (n = 21), did not possess higher nAb responses against heterologous envelopes (P = 0.46) or their mothers’ variants (P = 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P = 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P = 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P = 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity. IMPORTANCE Passive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby.
format	article
author	Melissa Ghulam-Smith Alex Olson Laura F. White Charles S. Chasela Sascha R. Ellington Athena P. Kourtis Denise J. Jamieson Gerald Tegha Charles M. van der Horst Manish Sagar
author_facet	Melissa Ghulam-Smith Alex Olson Laura F. White Charles S. Chasela Sascha R. Ellington Athena P. Kourtis Denise J. Jamieson Gerald Tegha Charles M. van der Horst Manish Sagar
author_sort	Melissa Ghulam-Smith
title	Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
title_short	Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
title_full	Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
title_fullStr	Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
title_full_unstemmed	Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
title_sort	maternal but not infant anti-hiv-1 neutralizing antibody response associates with enhanced transmission and infant morbidity
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/9a80cb0441ee479eb38999a0594d3b71
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Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity

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