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

Georgia D. Tomaras*, Guido Ferrari, Xiaoying Shen, S. Munir Alam, Hua Xin Liao, Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Youyi Fong, Xi Chen, Brigid Poling, Cindo O. Nicholson, Ruijun Zhang, Xiaozhi Lu, Robert Parks, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Peter B. GilbertJerome H. Kim, Nelson L. Michael, David C. Montefiori, Barton F. Haynes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

337 Scopus citations


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 correlatedwith 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 IgGresponses throughcompetitionfor thesameEnvbinding 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.

Original languageEnglish
Pages (from-to)9019-9024
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - 28 May 2013
Externally publishedYes


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