Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2013-05, Vol.110 (22), p.9019-9024

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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.