Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding
HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence
vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against
HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal
antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and
antigens including variable one and two loop scaffold
antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144
vaccine recipients, who were randomized to receive two late boosts of
ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or
ALVAC-HIV alone at 0 and 6 months. Late
vaccine boosting increased
IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and
ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS.
IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and
ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold) and SP (2 fold) two weeks post first boost.
IgG to Case A2 was only detected in AIDSVAX®B/E and
ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal
IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma
IgG levels (p<0.001). Although the magnitude of
IgG responses declined after boosting, anti-gp120 A244gD
IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific
antibodies (
IgG and dimeric
IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.