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.
Schneider
John A
JA
Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA.
Alam
Shaheen A
SA
Ackers
Marta
M
Parekh
Bharat
B
Chen
Hua Yun
HY
Graham
Parrie
P
Gurwith
Marc
M
Mayer
Kenneth
K
Novak
Richard M
RM
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D002584:Cervix Uteri / Q000276:immunology*; D002641:Chicago; D005260:Female; D005881:Gingiva / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D018023:HIV Seronegativity; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology; D016017:Odds Ratio; D012307:Risk Factors; D012309:Risk-Taking; D007507:Therapeutic Irrigation; D013997:Time Factors; D016896:Treatment Outcome; D047568:Unsafe Sex
D016915:AIDS Vaccines; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G