HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.

Identifying naturally-occurring neutralizing antibodies (NAb) that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb...

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Autores principales:	Valerie Cortez, Katherine Odem-Davis, R Scott McClelland, Walter Jaoko, Julie Overbaugh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2c3ddf0227d24015a58bd843a3f4989c
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spelling	oai:doaj.org-article:2c3ddf0227d24015a58bd843a3f4989c2021-11-18T06:04:36ZHIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.1553-73661553-737410.1371/journal.ppat.1002611https://doaj.org/article/2c3ddf0227d24015a58bd843a3f4989c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479183/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Identifying naturally-occurring neutralizing antibodies (NAb) that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb breadth has previously been shown to be positively associated with viral diversity. Therefore, we hypothesized that superinfected individuals develop a broad NAb response as a result of increased antigenic stimulation by two distinct viruses. To test this hypothesis, plasma samples from 12 superinfected women each assigned to three singly infected women were tested against a panel of eight viruses representing four different HIV-1 subtypes at matched time points post-superinfection (~5 years post-initial infection). Here we show superinfected individuals develop significantly broader NAb responses post-superinfection when compared to singly infected individuals (RR = 1.68, CI: 1.23-2.30, p = 0.001). This was true even after controlling for NAb breadth developed prior to superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both unadjusted and adjusted analyses showed significantly greater potency in superinfected cases compared to controls. Notably, two superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1∶300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth was detected within a year of superinfection in both of these individuals, which was within 1.5 years of their initial infection. These data suggest that sequential infections lead to augmentation of the NAb response, a process that may provide insight into potential mechanisms that contribute to the development of antibody breadth. Therefore, a successful vaccination strategy that mimics superinfection may lead to the development of broad NAbs in immunized individuals.Valerie CortezKatherine Odem-DavisR Scott McClellandWalter JaokoJulie OverbaughPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 3, p e1002611 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Valerie Cortez Katherine Odem-Davis R Scott McClelland Walter Jaoko Julie Overbaugh HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
description	Identifying naturally-occurring neutralizing antibodies (NAb) that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb breadth has previously been shown to be positively associated with viral diversity. Therefore, we hypothesized that superinfected individuals develop a broad NAb response as a result of increased antigenic stimulation by two distinct viruses. To test this hypothesis, plasma samples from 12 superinfected women each assigned to three singly infected women were tested against a panel of eight viruses representing four different HIV-1 subtypes at matched time points post-superinfection (~5 years post-initial infection). Here we show superinfected individuals develop significantly broader NAb responses post-superinfection when compared to singly infected individuals (RR = 1.68, CI: 1.23-2.30, p = 0.001). This was true even after controlling for NAb breadth developed prior to superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both unadjusted and adjusted analyses showed significantly greater potency in superinfected cases compared to controls. Notably, two superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1∶300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth was detected within a year of superinfection in both of these individuals, which was within 1.5 years of their initial infection. These data suggest that sequential infections lead to augmentation of the NAb response, a process that may provide insight into potential mechanisms that contribute to the development of antibody breadth. Therefore, a successful vaccination strategy that mimics superinfection may lead to the development of broad NAbs in immunized individuals.
format	article
author	Valerie Cortez Katherine Odem-Davis R Scott McClelland Walter Jaoko Julie Overbaugh
author_facet	Valerie Cortez Katherine Odem-Davis R Scott McClelland Walter Jaoko Julie Overbaugh
author_sort	Valerie Cortez
title	HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
title_short	HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
title_full	HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
title_fullStr	HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
title_full_unstemmed	HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.
title_sort	hiv-1 superinfection in women broadens and strengthens the neutralizing antibody response.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2c3ddf0227d24015a58bd843a3f4989c
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HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response.

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