Table 2. Correlates of protection: lessons learned in human efficacy trials.

Vax004: No prevention of HIV acquisition or disease progression
High neutralizing antibody levels against MN strain inversely correlated with HIV incidence
ADCVI correlated inversely with the rate of acquiring HIV infection
ADCVI correlated poorly with neutralizing or CD4-gp120-blocking antibody activity and was modulated by FcR polymorphisms
Vax003: No prevention of HIV acquisition or disease progression
No correlate whatsoever identified
Step (HVTN 502) and Phambili (HVTN 503): No prevention of HIV acquisition or disease progression
Sieve analysis showed evidence of vaccine-elicited immune pressure on the founder virus though no specific CD8+ CTL recognizing that epitope could be identified
Vaccinees with HLA alleles associated with HIV-1 control had a significantly lower mean viral load
HVTN 505: No prevention of HIV acquisition or disease progression
Analysis on going
RV144: 31.2% efficacy for HIV acquisition at 42 mo, 60% at 12 mo. No prevention of disease progression
Plasma IgG binding antibody to scaffolded gp70 V1V2 envelope proteins and V3 peptide correlated inversely with risk of infection (high antibody level correlated with lower rate of infection.) Env IgG3 antibodies correlate inversely with risk of infection.
Env plasma IgA correlated directly with higher rate of infection
Low levels of Env-specific IgA antibodies, IgG avidity, ADCC, neutralizing antibodies, and Env-specific CD4+ T cells, were inversely correlated with higher rate of infection. Plasma Env IgA can block ADCC.
Sieve analysis identified 2 vaccine-associated genetic signatures in V2 corresponding to sites 169 and 181, further supporting the hypothesis that vaccination-induced immune responses directed against the V2 loop were associated with protection. Sieve analysis identified a V3 signature suggesting a potential role of V3 antibodies in protection.
V2-specific antibodies can mediate ADCC, neutralization and low-level virus capture FcγRIIC polymorphism is associated with vaccine efficacy and correlates of HIV-1 infection risk
Exploration of mucosal immune responses on going in follow-up Phase II trials