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Zolla-Pazner Susan; Williams, Constance; deCamp, Allan; Morris, Daryl; Haynes, Barton; Kim, Jerome; Michael, Nelson; Rao, Mangala
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2012
doi: 10.1097/01.qai.0000413733.06987.08

ObjectiveDetermine the role of V2 antibodies (Abs) in protecting vaccinees from HIV infection after immunization with ALVAC/HIV and clade E and B recombinant gp120 (RV144 vaccine regimen). ELISA reactivity to a V1V2-gp70 fusion protein and a cyclic V2 peptide was assessed using coded plasma specimens from RV144 participants. Results showed that Ab responses were divided into tertiles (low, medium and high). Vaccinees with a high level of Abs to V1V2-gp70 had a lower rate of HIV infection than did those with a low level of Abs. Multivariate logistic regression analysis showed an estimated 71% reduction in the infecton rate for vaccinees with high vs vaccinees with low Ab responses to V1V2-gp70 (P = 0.02). Similarly, compared to the entire placebo group that was HIV- at 26 weeks, the estimated Vaccine Efficacy (VE) was 3% (P = 0.91) for subjects with a low V1V2 Ab response, while the estimated VE was 58% (P = 0.02) for vaccinees with high V1V2 Abs. The Abs measured by this assay appear to be specific for V2 because no V1 Abs were detected, and epitope mapping data suggest that the epitope recognized by vaccinees' Abs target the mid-loop region of V2. There was no statistically significant correlation between infection rate and Abs reactive with a cyclic V2 peptide containing the entire V2 loop of the clade E A244 strain. In the primary case control analysis the Ab response to V1V2-gp70 was statistically significantly inversely correlated with infection. While secondary analyses suggest that other immunologic responses (including Abs to other epitopes and cellular responses) may also play a role in protection, the data most strongly support the hypothesis that V2 Abs are important for protection.

© 2012 Lippincott Williams & Wilkins, Inc.