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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34835
Title: FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial
Authors: 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
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
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: Journal of Clinical Investigation. Vol.124, No.9 (2014), 3879-3890
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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84907014639&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34835
ISSN: 15588238
00219738
Appears in Collections:Scopus 2011-2015

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