Influence of exogenous reproductive hormones on specific antibody production in genital secretions after vaginal vaccination with recombinant cholera toxin B subunit in humans

Abstract

The objective of this study was to investigate the influence of exogenous reproductive hormones on the local and systemic production of specific immunoglobulin A (IgA) and IgG antibodies after vaginal vaccination with recombinant cholera toxin subunit B (CTB). Three groups of women using either progesterone-containing intrauterine devices (n=9), oral contraceptives (n=8), or no hormonal contraceptive methods (n=9) were vaginally immunized twice, 2 weeks apart. Cervical secretions, vaginal fluids, and serum were collected before and after vaccination. Total and CTB-specific IgA and IgG antibodies in genital secretions and serum were analyzed by enzyme-linked immunosorbent assay. A majority of the women presented strong CTB-specific IgA and IgG antibody responses in cervicovaginal secretions after vaccination, whereas the antitoxin responses in serum were weaker. Exogenously administered steroid hormones did not seem to have any impact on the production of specific antibodies. Both the frequencies and the magnitudes of IgA and IgG antitoxin responses in genital secretions were comparable among the three immunization groups. An association, in particular for IgA, was found between the magnitudes of the CTB-specific antibody responses in cervical secretions and vaginal fluids after vaccination. The sensitivities and positive predictive values of vaginal antibody analyses to reflect responses in cervical secretions were also high, suggesting that vaginal fluids alone might be used for evaluation of genital immune responses in large-scale vaccination studies in the future.

FIG. 1.

Antitoxin antibody responses in cervical secretions after two vaginal doses of recombinant CTB in women using different types of contraceptive methods. The numbers of responders are given below the x axes. Responders were defined as having a >2-fold increase in the ratio of the CTB-specific antibody titer to the total-immunoglobulin concentration between pre- and postvaccination specimens.

FIG. 2.

Antitoxin antibody responses in vaginal fluids after two vaginal doses of recombinant CTB in women using different types of contraceptive methods. The numbers of responders are given below the x axes. Responders were defined as having a >2-fold increase in the ratio of the CTB-specific antibody titer to the total-immunoglobulin concentration between pre- and postvaccination specimens. Specimens from one volunteer in the OCP group contained too low IgA and IgG concentrations (≤40 μg ml⁻¹) and were therefore excluded from further analyses.

FIG. 3.

Association between increases in CTB-specific IgA antibody titers per total-IgA levels in cervical secretions and corresponding increases in vaginal fluids from 25 volunteers after two vaginal immunizations with recombinant CTB.