A recombinant multivalent combination vaccine protects againstChlamydiaand genital herpes

Abstract

Chlamydia trachomatis and Herpes simplex virus type 2 (HSV-2) genital infections pose a considerable public health challenge worldwide. Considering the high incidence of coinfections by the two pathogens, a combination vaccine that can be administered as a single regimen would be highly desirable. Recombinant Vibrio cholerae ghosts (rVCG) offer an attractive approach for the induction of humoral and cellular immune responses against human and animal pathogens. In this study, we evaluated a bivalent combination vaccine formulation comprising rVCG expressing chlamydial MOMP and HSV-2 glycoprotein D in mice for immunogenicity and protective efficacy against genital challenge with either pathogen. Mice immunized with the combination vaccine elicited secretory IgA and IgG2a antibodies to both chlamydial and HSV-2 antigens in serum and vaginal secretions. Robust antigen-specific mucosal and systemic T helper type 1 responses were induced in mice as measured by increased interferon-gamma levels produced by immune T cells in response to restimulation with target antigen in vitro. In addition, mice immunized with the combination vaccine were prophylactically protected from genital challenge with high doses of live Chlamydia and HSV-2. Thus, the combination vaccine regimen delivered by rVCG elicited adequate immune effectors that simultaneously protected against the individual pathogens.

Rectal administration of a chlamydial subunit vaccine protects against genital infection and upper reproductive tract pathology in mice

“…The amount of chlamydial PmpD-specific antibodies (IgG2c and IgA) in pooled serum and vaginal wash samples collected 2 weeks postimmunization was measured by a standard ELISA procedure described previously [29]. Briefly, Maxisorb 96-well plates (Costar) were coated overnight with 10 microgram/ml of a synthesized 15-amino acid conserved PmpD peptide (Syd Labs, Malden, MA) in PBS.…”

Exploiting cholera vaccines as a versatile antigen delivery platform

“…The VCG platform has recently been investigated as a carrier and delivery system for multiple Chlamydia trachomatis proteins, eliciting Chlamydia-specific protective immunity (Eko et al 2004;Ifere et al 2007). In addition, a rVCG-based combination vaccine comprising chlamydial major outer membrane protein and glycoprotein D of Herpes simplex virus 2 (HSV-2) elicited adequate Th1-associated immune effectors that simultaneously protected mice from genital challenge with high doses of live Chlamydia and HSV-2 (Macmillan et al 2007). These results clearly place the VCG system as a promising alternative to current cholera vaccines and an effective antigen delivery system.…”

Development of aChlamydia trachomatisbacterial ghost vaccine to fight human blindness

“…A multisubunit vaccine consisting of VCG co-expressing multiple chlamydial outer membrane proteins induced higher frequency of Th1 cells and relatively greater ability to confer protective immunity compared to single subunit constructs. [62][63][64] A major advantage of the multiple subunit approach is the potential synergistic immunologic benefit of a combination of epitopes from multiple antigens, which will likely induce a higher frequency of immune effectors that ensures an effective long-lasting immunity. In addition to their delivery capacity, VCG provide adjuvant functions to the foreign delivered antigens as additional adjuvants were not needed to induce immune responses.…”

“…65 Recently, a VCG-based combination vaccine comprising chlamydial MOMP and glycoprotein D (gD2) of HSV-2 elicited adequate Th1-associated immune effectors that simultaneously protected mice from genital challenge with high doses of live Chlamydia and HSV-2. 64 Results from these studies have contributed to the current paradigm that protective immunity against Chlamydia is a function of the level of Th1 response elicited. These results clearly indicate that the VCG system is an effective vaccine delivery system and a promising alternative to current vaccine design approaches.…”