Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.

<h4>Unlabelled</h4>In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from di...

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Autores principales: Susan Zolla-Pazner, Allan deCamp, Peter B Gilbert, Constance Williams, Nicole L Yates, William T Williams, Robert Howington, Youyi Fong, Daryl E Morris, Kelly A Soderberg, Carmela Irene, Charles Reichman, Abraham Pinter, Robert Parks, Punnee Pitisuttithum, Jaranit Kaewkungwal, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Charla Andrews, Robert J O'Connell, Zhi-yong Yang, Gary J Nabel, Jerome H Kim, Nelson L Michael, David C Montefiori, Hua-Xin Liao, Barton F Haynes, Georgia D Tomaras
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spelling oai:doaj.org-article:908050f48a3743e69cae612588e666782021-11-18T08:33:56ZVaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.1932-620310.1371/journal.pone.0087572https://doaj.org/article/908050f48a3743e69cae612588e666782014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24504509/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.<h4>Trial registration</h4>ClinicalTrials.gov NCT00223080.Susan Zolla-PaznerAllan deCampPeter B GilbertConstance WilliamsNicole L YatesWilliam T WilliamsRobert HowingtonYouyi FongDaryl E MorrisKelly A SoderbergCarmela IreneCharles ReichmanAbraham PinterRobert ParksPunnee PitisuttithumJaranit KaewkungwalSupachai Rerks-NgarmSorachai NitayaphanCharla AndrewsRobert J O'ConnellZhi-yong YangGary J NabelJerome H KimNelson L MichaelDavid C MontefioriHua-Xin LiaoBarton F HaynesGeorgia D TomarasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87572 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Susan Zolla-Pazner
Allan deCamp
Peter B Gilbert
Constance Williams
Nicole L Yates
William T Williams
Robert Howington
Youyi Fong
Daryl E Morris
Kelly A Soderberg
Carmela Irene
Charles Reichman
Abraham Pinter
Robert Parks
Punnee Pitisuttithum
Jaranit Kaewkungwal
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Charla Andrews
Robert J O'Connell
Zhi-yong Yang
Gary J Nabel
Jerome H Kim
Nelson L Michael
David C Montefiori
Hua-Xin Liao
Barton F Haynes
Georgia D Tomaras
Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
description <h4>Unlabelled</h4>In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.<h4>Trial registration</h4>ClinicalTrials.gov NCT00223080.
format article
author Susan Zolla-Pazner
Allan deCamp
Peter B Gilbert
Constance Williams
Nicole L Yates
William T Williams
Robert Howington
Youyi Fong
Daryl E Morris
Kelly A Soderberg
Carmela Irene
Charles Reichman
Abraham Pinter
Robert Parks
Punnee Pitisuttithum
Jaranit Kaewkungwal
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Charla Andrews
Robert J O'Connell
Zhi-yong Yang
Gary J Nabel
Jerome H Kim
Nelson L Michael
David C Montefiori
Hua-Xin Liao
Barton F Haynes
Georgia D Tomaras
author_facet Susan Zolla-Pazner
Allan deCamp
Peter B Gilbert
Constance Williams
Nicole L Yates
William T Williams
Robert Howington
Youyi Fong
Daryl E Morris
Kelly A Soderberg
Carmela Irene
Charles Reichman
Abraham Pinter
Robert Parks
Punnee Pitisuttithum
Jaranit Kaewkungwal
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Charla Andrews
Robert J O'Connell
Zhi-yong Yang
Gary J Nabel
Jerome H Kim
Nelson L Michael
David C Montefiori
Hua-Xin Liao
Barton F Haynes
Georgia D Tomaras
author_sort Susan Zolla-Pazner
title Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
title_short Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
title_full Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
title_fullStr Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
title_full_unstemmed Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
title_sort vaccine-induced igg antibodies to v1v2 regions of multiple hiv-1 subtypes correlate with decreased risk of hiv-1 infection.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/908050f48a3743e69cae612588e66678
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