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

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'ConnellZhi Yong Yang, Gary J. Nabel, Jerome H. Kim, Nelson L. Michael, David C. Montefiori, Hua Xin Liao, Barton F. Haynes, Georgia D. Tomaras

Research output: Contribution to journalArticle

Abstract

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. Trial Registration: ClincialTrials.gov NCT00223080.

Original languageEnglish (US)
Article numbere87572
JournalPLoS One
Volume9
Issue number2
DOIs
StatePublished - Feb 4 2014
Externally publishedYes

Fingerprint

risk reduction
Human immunodeficiency virus 1
HIV Infections
HIV-1
Vaccines
Immunoglobulin G
vaccines
Antigens
Scaffolds
antibodies
Antibodies
infection
antigens
AIDS Vaccines
Assays
Logistic Models
HIV Envelope Protein gp120
Logistics
scaffolding proteins
Glycoproteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zolla-Pazner, S., DeCamp, A., Gilbert, P. B., Williams, C., Yates, N. L., Williams, W. T., ... Tomaras, G. D. (2014). Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS One, 9(2), [e87572]. https://doi.org/10.1371/journal.pone.0087572

Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. / Zolla-Pazner, Susan; DeCamp, Allan; Gilbert, Peter B.; Williams, Constance; Yates, Nicole L.; Williams, William T.; Howington, Robert; Fong, Youyi; Morris, Daryl E.; Soderberg, Kelly A.; Irene, Carmela; Reichman, Charles; Pinter, Abraham; Parks, Robert; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Andrews, Charla; O'Connell, Robert J.; Yang, Zhi Yong; Nabel, Gary J.; Kim, Jerome H.; Michael, Nelson L.; Montefiori, David C.; Liao, Hua Xin; Haynes, Barton F.; Tomaras, Georgia D.

In: PLoS One, Vol. 9, No. 2, e87572, 04.02.2014.

Research output: Contribution to journalArticle

Zolla-Pazner, S, DeCamp, A, Gilbert, PB, Williams, C, Yates, NL, Williams, WT, Howington, R, Fong, Y, Morris, DE, Soderberg, KA, Irene, C, Reichman, C, Pinter, A, Parks, R, Pitisuttithum, P, Kaewkungwal, J, Rerks-Ngarm, S, Nitayaphan, S, Andrews, C, O'Connell, RJ, Yang, ZY, Nabel, GJ, Kim, JH, Michael, NL, Montefiori, DC, Liao, HX, Haynes, BF & Tomaras, GD 2014, 'Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection', PLoS One, vol. 9, no. 2, e87572. https://doi.org/10.1371/journal.pone.0087572
Zolla-Pazner, Susan ; DeCamp, Allan ; Gilbert, Peter B. ; Williams, Constance ; Yates, Nicole L. ; Williams, William T. ; Howington, Robert ; Fong, Youyi ; Morris, Daryl E. ; Soderberg, Kelly A. ; Irene, Carmela ; Reichman, Charles ; Pinter, Abraham ; Parks, Robert ; Pitisuttithum, Punnee ; Kaewkungwal, Jaranit ; Rerks-Ngarm, Supachai ; Nitayaphan, Sorachai ; Andrews, Charla ; O'Connell, Robert J. ; Yang, Zhi Yong ; Nabel, Gary J. ; Kim, Jerome H. ; Michael, Nelson L. ; Montefiori, David C. ; Liao, Hua Xin ; Haynes, Barton F. ; Tomaras, Georgia D. / Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. In: PLoS One. 2014 ; Vol. 9, No. 2.
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abstract = "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. Trial Registration: ClincialTrials.gov NCT00223080.",
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AU - Yates, Nicole L.

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AU - Irene, Carmela

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AU - Rerks-Ngarm, Supachai

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AU - Andrews, Charla

AU - O'Connell, Robert J.

AU - Yang, Zhi Yong

AU - Nabel, Gary J.

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AU - Michael, Nelson L.

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