TY - JOUR
T1 - Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG
AU - Tomaras, Georgia D.
AU - Ferrari, Guido
AU - Shen, Xiaoying
AU - Alam, S. Munir
AU - Liao, Hua Xin
AU - Pollara, Justin
AU - Bonsignori, Mattia
AU - Moody, M. Anthony
AU - Fong, Youyi
AU - Chen, Xi
AU - Poling, Brigid
AU - Nicholson, Cindo O.
AU - Zhang, Ruijun
AU - Lu, Xiaozhi
AU - Parks, Robert
AU - Kaewkungwal, Jaranit
AU - Nitayaphan, Sorachai
AU - Pitisuttithum, Punnee
AU - Rerks-Ngarm, Supachai
AU - Gilbert, Peter B.
AU - Kim, Jerome H.
AU - Michael, Nelson L.
AU - Montefiori, David C.
AU - Haynes, Barton F.
PY - 2013/5/28
Y1 - 2013/5/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84878430727
U2 - 10.1073/pnas.1301456110
DO - 10.1073/pnas.1301456110
M3 - Article
C2 - 23661056
AN - SCOPUS:84878430727
SN - 0027-8424
VL - 110
SP - 9019
EP - 9024
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -