Evaluation of a multisubunit recombinant polymorphic membrane protein and major outer membrane protein T cell vaccine against Chlamydia muridarum genital infection in three strains of mice

Abstract

An efficacious vaccine is needed to control Chlamydia trachomatis infection. In the murine model of C. muridarum genital infection, multifunctional mucosal CD4 T cells are the foundation for protective immunity, with antibody playing a secondary role. We previously identified four Chlamydia outer membrane proteins (PmpE, PmpF, PmpG and PmpH) as CD4 T cell vaccine candidates using a dendritic cell-based immunoproteomic approach. We also demonstrated that these four polymorphic membrane proteins (Pmps) individually conferred protection as measured by accelerated clearance of Chlamydia infection in the C57BL/6 murine genital tract model. The major outer membrane protein, MOMP is also a well-studied protective vaccine antigen in this system. In the current study, we tested immunogenicity and protection of a multisubunit recombinant protein vaccine consisting of the four Pmps (PmpEFGH) with or without the major outer membrane protein (MOMP) formulated with a Th1 polarizing adjuvant in C57BL/6, Balb/c and C3H mice. We found that C57BL/6 mice vaccinated with PmpEFGH+MOMP elicited more robust cellular immune responses than mice immunized with individual protein antigens. Pmps elicited more variable cellular immune responses than MOMP among the three strains of mice. The combination vaccine accelerated clearance in the three strains of mice although at different rates. We conclude that the recombinant outer membrane protein combination constitutes a promising first generation Chlamydia vaccine construct that should provide broad immunogenicity in an outbred population.

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

“…However combination of both antigens may be an ideal Chlamydia vaccine. Our studies demonstrate that a recombinant protein vaccine consisting of four Pmps (PmpEFGH) with MOMP formulated with a Th1 polarizing adjuvant significantly accelerated clearance in the C57BL/6 mouse C. trachomatis transcervical infection model [53] and in the C. muridarum genital infection mouse model using mice of different MHC backgrounds [69]. Overall we suggest that Chlamydia outer membrane proteins are likely to be the most important T cell antigens useful in the development of a C. trachomatis subunit vaccine.…”

Chlamydial polymorphic membrane proteins: regulation, function and potential vaccine candidates

“…Indeed, several studies have investigated the efficacy of various Pmps to protect against Chlamydia infection and activate T cells. [86][87][88][89][90][91] Using affinity chromatography and tandem mass spectrometry, Karunakaran et al demonstrated that dendritic cells infected with C. muridarum presented PmpG and F on their MHC class II receptors. Furthermore, purified Chlamydia-specific CD4+ T cells produced high levels of INF-g after co-culture with the previously C. muridarum-infected dendritic cells suggesting T cell recognition of the MHC class-II bound Pmps.…”

“…They also showed that PmpE and H have low stimulatory capabilities to induce IFN-g production in CD4+ T cells and therefore may not be suited for use in a chlamydial multisubunit vaccine. 90 C. trachomatis PmpG has also been used as an epitope in conjunction with vault nanoparticles. These studies demonstrated that a PmpG-vault nanoparticle vaccine incubated with a human monocyte cell line (THP-1) activated the protease caspase-1 and IL-1b production.…”

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

“…Therefore, the T cell antigens processed by CPAF and identified in the current study should be further validated during in vivo infection in the future. In addition, identifying specific T cell antigens through the dendritic cell-based immunopretomic approach is considered a promising way to research a chlamydia vaccine [39,58], and several promising T cell antigens were identified to be likely candidates for vaccine but require further validation. In this study, we took advantage of this system to identify several T cells antigens and we further investigated whether CPAF blocks the presentation of these T cells antigens.…”