Immune correlates of vaccine protection against HIV-1 acquisition

Abstract

The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4(+) T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition.

Figure 1. Kinetics of vaccine induced antibody response and vaccine protection in RV144

Schematic representation of selected immune responses to vaccination with RV144 regimen ALVAC (pox) followed by gp120 (protein).

Figure 2. Estimated vaccine efficacy in RV144

Estimated vaccine efficacy in RV144 as a function of the level of IgG binding antibody to gp70-scaffolded V1V2 in a model assuming VE of 0% in vaccinees with no V1V2 antibodies (black line) and the distribution of IgG levels among vaccinees (histogram) (Panel A). Kaplan-Meir curve of the probability of acquiring HIV infection in vaccine recipients with Low, Medium and High V1V2-scaffold IgG Ab responses, measured by BAMA at Week 26 (Panel B). The median, upper, and lower bounds of antibody concentrations to 3 of the V1V2 antigens that were correlated to vaccine efficacy: the left panel shows the cross-clade clade B gp70 levels; the middle panel the V1V2 response to the AE isolate in the ALVAC vector used in RV144; and the third panel shows the V1V2 responses to the AE gp120 used in the protein boost in RV144 (Panel C).