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Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 May 28; Vol. 110 (22), pp. 9019-24. Date of Electronic Publication: 2013 May 09. - Publication Year :
- 2013
-
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.
- Subjects :
- Antibodies, Monoclonal
Binding, Competitive genetics
Enzyme-Linked Immunosorbent Assay
Humans
Immunoglobulin A immunology
Kinetics
Logistic Models
Risk Assessment
Surface Plasmon Resonance
AIDS Vaccines immunology
HIV Envelope Protein gp120 immunology
Immunoglobulin A blood
Immunoglobulin G metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 110
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 23661056
- Full Text :
- https://doi.org/10.1073/pnas.1301456110