Mucosal HIV-binding antibody and neutralizing activity in high-risk HIV-uninfected female participants in a trial of HIV-vaccine efficacy.

BACKGROUND This study investigated gp120-binding antibody and neutralizing activity, at the gingival- and cervical-mucosal levels, in response to a bivalent gp120 candidate vaccine. METHODS Women who met the study's inclusion criteria for documented high-risk behaviors participated in a nested substudy of the multicenter phase 3 trial of human immunodeficiency virus (HIV)-vaccine efficacy, VAX004. Gingival, cervicovaginal lavage, and plasma specimens were collected at 6-month intervals for 3 years. Binding-antibody and neutralizing-activity assays quantified the presence of anti-HIV activity in mucosal specimens. RESULTS Vaccine recipients were more likely than placebo recipients to have IgG binding antibodies in all 3 compartments tested and to have only IgA binding antibody in plasma (P<.0001). The relationship between vaccine and cervicovaginal IgG achieved significance (odds ratio [OR], 6.6 [P=.01]) but was weakened by the presence of cervicovaginal leukocytes. There was no relationship between immunization and the presence of neutralizing activity, in either bivariate or multivariate modeling (OR, 6.0 [P=.29]). CONCLUSIONS Vaccination is associated with the presence of both gp120-binding IgG in all compartments and plasma IgA but not with neutralizing activity. There is a role for the measurement of mucosal immunity in response to candidate vaccines and, in particular, for a determination of HIV-specific neutralizing antibodies.