Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG

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...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 110; H. 22; S. 9019
Hauptverfasser: Tomaras, Georgia D, Ferrari, Guido, Shen, Xiaoying, Alam, S Munir, Liao, Hua-Xin, Pollara, Justin, Bonsignori, Mattia, Moody, M Anthony, Fong, Youyi, Chen, Xi, Poling, Brigid, Nicholson, Cindo O, Zhang, Ruijun, Lu, Xiaozhi, Parks, Robert, Kaewkungwal, Jaranit, Nitayaphan, Sorachai, Pitisuttithum, Punnee, Rerks-Ngarm, Supachai, Gilbert, Peter B, Kim, Jerome H, Michael, Nelson L, Montefiori, David C, Haynes, Barton F
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 28.05.2013
Schlagworte:
AIDS Vaccines - immunology
Antibodies, Monoclonal
Binding, Competitive - genetics
Enzyme-Linked Immunosorbent Assay
HIV Envelope Protein gp120 - immunology
Humans
Immunoglobulin A - blood
Immunoglobulin A - immunology
Immunoglobulin G - metabolism
Kinetics
Logistic Models
Risk Assessment
Surface Plasmon Resonance
ISSN:1091-6490, 1091-6490
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1301456110