Publication:
FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial

Issued Date

2014-01-01

Resource Type

Article

ISSN

15588238
00219738

DOI

10.1172/JCI75539

Other identifier(s)

2-s2.0-84907014639

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Journal of Clinical Investigation. Vol.124, No.9 (2014), 3879-3890

Suggested Citation

Shuying S. Li, Peter B. Gilbert, Georgia D. Tomaras, Gustavo Kijak, Guido Ferrari, Rasmi Thomas, Chul Woo Pyo, Susan Zolla-Pazner, David Montefiori, Hua Xin Liao, Gary Nabel, Abraham Pinter, David T. Evans, Raphael Gottardo, James Y. Dai, Holly Janes, Daryl Morris, Youyi Fong, Paul T. Edlefsen, Fusheng Li, Nicole Frahm, Michael D. Alpert, Heather Prentice, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Merlin L. Robb, Robert J. O'Connell, Barton F. Haynes, Nelson L. Michael, Jerome H. Kim, M. Juliana McElrath, Daniel E. Geraghty FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial. Journal of Clinical Investigation. Vol.124, No.9 (2014), 3879-3890. doi:10.1172/JCI75539 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34835

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Title

FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial

Author(s)

Shuying S. Li
 Peter B. Gilbert
 Georgia D. Tomaras
 Gustavo Kijak
 Guido Ferrari
 Rasmi Thomas
 Chul Woo Pyo
 Susan Zolla-Pazner
 David Montefiori
 Hua Xin Liao
 Gary Nabel
 Abraham Pinter
 David T. Evans
 Raphael Gottardo
 James Y. Dai
 Holly Janes
 Daryl Morris
 Youyi Fong
 Paul T. Edlefsen
 Fusheng Li
 Nicole Frahm
 Michael D. Alpert
 Heather Prentice
 Supachai Rerks-Ngarm
 Punnee Pitisuttithum
 Jaranit Kaewkungwal
 Sorachai Nitayaphan
 Merlin L. Robb
 Robert J. O'Connell
 Barton F. Haynes
 Nelson L. Michael
 Jerome H. Kim
 M. Juliana McElrath
 Daniel E. Geraghty

Other Contributor(s)

Fred Hutchinson Cancer Research Center
 Duke University School of Medicine
 Walter Reed Army Institute of Research
 NYU School of Medicine
 Global RandD
 Rutgers New Jersey Medical School
 University of Wisconsin Madison
 Harvard Medical School
 Thailand Ministry of Public Health
 Mahidol University
 Royal Thai Army

Abstract

The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1-specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor-mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one FCGR2C tag SNP (rs114945036) that associated with VE against HIV-1 subtype CRF01-AE, with lysine at position 169 (169K) in the V2 loop (CRF01-AE 169K). Individuals carrying CC in this SNP had an estimated VE of 15%, while individuals carrying CT or TT exhibited a VE of 91%. Furthermore, the rs114945036 SNP was highly associated with 3 other FCGR2C SNPs (rs138747765, rs78603008, and rs373013207). Env-specific IgG and IgG3 Abs, IgG avidity, and neutralizing Abs inversely correlated with CRF01-AE 169K HIV-1 infection risk in the CT- or TTcarrying vaccine recipients only. These data suggest a potent role of Fc-γ receptors and Fc-mediated Ab function in conferring protection from transmission risk in the RV144 VE trial.

Keyword(s)

Medicine

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URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/34835

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