title: Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.
abstract: Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlated with risk, whereas HIV-1 Env-specific plasma IgA responses directly correlated with risk. In the secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate of risk, but only in the presence of low plasma IgA Env-specific antibodies. Thus, we investigated the hypothesis that IgA could attenuate the protective effect of IgG responses through competition for the same Env binding sites. We report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. Moreover, Env-specific IgA antibodies from RV144 vaccinees blocked the binding of ADCC-mediating mAb to HIV-1 Env glycoprotein 120 (gp120). An Env-specific monomeric IgA mAb isolated from an RV144 vaccinee also inhibited the ability of natural killer cells to kill HIV-1-infected CD4(+) T cells coated with RV144-induced IgG antibodies. We show that monomeric Env-specific IgA, as part of postvaccination polyclonal antibody response, may modulate vaccine-induced immunity by diminishing ADCC effector function.
authors: Duke Human Vaccine Institute, and Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. gdt@duke.edu
authors: Georgia D
authors: GD
authors: Tomaras
authors: Guido
authors: G
authors: Ferrari
authors: Xiaoying
authors: X
authors: Shen
authors: S Munir
authors: SM
authors: Alam
authors: Hua-Xin
authors: HX
authors: Liao
authors: Justin
authors: J
authors: Pollara
authors: Mattia
authors: M
authors: Bonsignori
authors: M Anthony
authors: MA
authors: Moody
authors: Youyi
authors: Y
authors: Fong
authors: Xi
authors: X
authors: Chen
authors: Brigid
authors: B
authors: Poling
authors: Cindo O
authors: CO
authors: Nicholson
authors: Ruijun
authors: R
authors: Zhang
authors: Xiaozhi
authors: X
authors: Lu
authors: Robert
authors: R
authors: Parks
authors: Jaranit
authors: J
authors: Kaewkungwal
authors: Sorachai
authors: S
authors: Nitayaphan
authors: Punnee
authors: P
authors: Pitisuttithum
authors: Supachai
authors: S
authors: Rerks-Ngarm
authors: Peter B
authors: PB
authors: Gilbert
authors: Jerome H
authors: JH
authors: Kim
authors: Nelson L
authors: NL
authors: Michael
authors: David C
authors: DC
authors: Montefiori
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D016015:Logistic Models; D018570:Risk Assessment; D020349:Surface Plasmon Resonance
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C514793:gp120 protein, Human immunodeficiency virus 1
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