Vaccine-induced human antibodies specific for the third variable region of HIV-1 gp120 impose immune pressure on infecting viruses

Abstract

© 2014 The Authors. To evaluate the role of V3-specific IgG+antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reducedHIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactivewith cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough virusesfrom 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruseswith amino acids mismatching the vaccine at V3 site 317 (p= 0.004) and 52% against virusesmatching the vaccineat V3 site 307 (p = 0.004). This analysis was supported by data showing that vaccinees' plasma Abs wereless reactive with I307when replaced with residues foundmore often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F317were less infectious, possibly due to the contribution of F317to optimalformation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immunepressure on infecting viruses and inform efforts to design an HIV vaccine.