title: FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial.
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 TT-carrying 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.
authors.forename: Shuying S
authors.initials: SS
authors.lastname: Li
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Gustavo
authors.initials: G
authors.lastname: Kijak
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Pyo
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Gary
authors.initials: G
authors.lastname: Nabel
authors.forename: Abraham
authors.initials: A
authors.lastname: Pinter
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.forename: James Y
authors.initials: JY
authors.lastname: Dai
authors.forename: Holly
authors.initials: H
authors.lastname: Janes
authors.forename: Daryl
authors.initials: D
authors.lastname: Morris
authors.forename: Youyi
authors.initials: Y
authors.lastname: Fong
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Michael D
authors.initials: MD
authors.lastname: Alpert
authors.forename: Heather
authors.initials: H
authors.lastname: Prentice
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics*; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines; C080572:Fc gamma receptor IIC; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D017452:Receptors, IgG; C514793:gp120 protein, Human immunodeficiency virus 1
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