Research ArticleHIV

Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination

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Science Translational Medicine  19 Mar 2014:
Vol. 6, Issue 228, pp. 228ra39
DOI: 10.1126/scitranslmed.3007730

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Env IgG3 Takes Center Stage

Only one HIV-1 vaccine trial (RV144), to date, has demonstrated some level of vaccine efficacy. IgG antibodies to the V1-V2 region of the HIV-1 envelope correlated with decreased HIV-1 risk. However, a previous vaccine trial (VAX003) also induced these types of antibodies but failed to demonstrate efficacy, thus raising the question about whether the quality of the V1-V2 IgG response and the context of other immune responses were important. Yates et al. report that these two trials did induce a qualitatively distinct antibody subclass response, with more V1V2 IgG3 responses and correlations with antiviral function induced by the partially efficacious RV144 vaccine regimen compared to the VAX003 vaccine regimen that lacks efficacy. The authors then demonstrated that these specific IgG3 antibodies correlated with a decreased risk of infection in a placebo-controlled, blinded study of RV144 vaccinees with and without subsequent HIV-1 infection. Vaccine-induced HIV-1 antibody subclass profiles, specifically Env IgG3, should be evaluated in future HIV-1 vaccine efficacy trials to further refine immune correlates of protection.