Induction of immune memory by a multisubunit chlamydial vaccine

Abstract

We tested the hypothesis that intramuscular immunization with a multisubunit chlamydial vaccine candidate will induce long lasting immune responses in mice. Accordingly, groups of female C57BL/6 mice were immunized intramuscularly with Vibrio cholerae ghosts (VCG) expressing the Poring B and polymorphic membrane protein-D proteins of C. trachomatis or a control antigen. Humoral and cell-mediated immune responses were evaluated following immunization and after live chlamydial infection. Immunization induced an anamnestic response characterized by chlamydial-specific IgG2a and IgA antibodies in sera and vaginal lavage as well as specific genital and splenic T cell responses. The results also revealed that the local mucosal and systemic cellular and humoral immune effectors induced in mice following immunization with the vaccine candidate are long lasting. Vaccinated mice cleared intravaginal challenge with 105 chlamydial inclusion forming units within 12 days compared to control mice, which shed up to 2×103 IFUs at this time point. Moreover, rechallenge of mice 98 days after resolution of the primary infection resulted in the recall and retention of a relatively high frequency of chlamydial-specific Th1 cells and IgG2a in the genital mucosa. These results provide the first evidence that a VCG-based multisubunit chlamydial vaccine is capable of effectively stimulating anamnestic systemic and mucosal immune responses in mice. The data support further vaccine evaluation and testing for induction of long-term protective immunity.

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…Numerous immunization routes have been used for chlamydial vaccinations, including oral (210), intranasal (211), intravaginal (139), subcutaneous (212), intramuscular (213), perivaginal (212), perisacral (212), sublingual (214), and colonic (124) routes. A study using purified MOMP with a Borrelia surface protein as an adjuvant demonstrated that in two different mouse strains, intramuscular-plus-subcutaneous and perivaginal-plus-perisacral immunization elicited high systemic and mucosal serum antibody titers.…”

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

“…The levels of systemic cytokine response in the mice were assayed by measuring Th1 (IFN-γ, TNF-α and T17) and Th2 (IL-5 and IL-10) cytokines in serum, at 4 wk after infection that resulted in infertility in the mice, as previously described [26]. Briefly, sera from blood samples (0.05 ml/mouse) were assayed for the indicated cytokines using the Bio-Plex cytokine assay kit in combination with the Bio-Plex Manager software (Bio-Rad, Hercules, CA), as previously described [26].…”

“…Briefly, sera from blood samples (0.05 ml/mouse) were assayed for the indicated cytokines using the Bio-Plex cytokine assay kit in combination with the Bio-Plex Manager software (Bio-Rad, Hercules, CA), as previously described [26]. The mean and SD of all replicate cultures were calculated.…”

“…The experiment was repeated three times. Determination of concentrations of Chlamydia-specific antibody isotypes (specifically IgG IgA) in sera measured by a standard ELI-SA procedure described previously [26]. Briefly, 96-well microtiter plates (Nunc Life Technologies, Rochester, NY) were coated with 10 µg/ml of chlamydial antigen (i.e., UV-inactivated elementary bodies) in 100 µl of PBS at 4 o C overnight.…”

Tubal Damage, Infertility and Tubal Ectopic Pregnancy: Chlamydia trachomatis and Other Microbial Aetiologies

“…These animal models have proved invaluable in providing knowledge of many novel candidate antigens for a vaccine (Barker et al, 2008;McNeilly et al, 2007;Murthy AK et al, 2011;Murthy et al, 2009) as well as novel delivery vehicles (Xu et al, 2011) and delivery routes such as oral and transcutaneous immunization for protection of genital infections (Hickey et al, 2010;Hickey et al, 2009) and have investigated a myriad of potential adjuvants (reviewed in Cochrane et al, 2010;Farris and Morrison, 2011; and immune responses elicited following animal immunization trials (Cunningham et al, 2011;McNeilly et al, 2007;Patton et al, 1983). For example it has recently been reported that a Vibrio cholerae ghost (VCG) multisubunit chlamydial vaccine delivered to mice by the intramuscular route stimulated immune memory in these animals (Eko et al, 2011). Protection correlates that have been assessed in these models to determine vaccine efficiency have included reduced shedding of viable chlamydial infectious bodies, reduced duration of infection and reduced tissue pathologies such as hydrosalpinx; a vaccine that can achieve one and/or any of these outcomes will greatly aid in diminishing the pathological sequelae of chlamydial genital infections.…”