Background: A vaccine for Chlamydia trachomatis is of urgent medical need. We explored bioinformatic approaches to generate an immunogen against C. trachomatis that would induce cross-serovar T cell responses as (i) CD4+ T cells have been shown in animal models and human studies to be important in chlamydial protection, and (ii) antibody responses may be restrictive and serovar-specific.

Methods: A consensus antigen based on over 1,500 MOMP sequences provided high epitope coverage against the most prevalent C. trachomatis strains in silico. Having designed the T cell immunogen, we assessed it for immunogenicity in prime-boost regimens. This consensus MOMP transgene was delivered using plasmid DNA, Human Adenovirus-5 (HuAd5) or modified vaccinia Ankara (MVA) vectors with or without MF59® adjuvanted recombinant MOMP protein.

Results: Different regimens induced distinct immune profiles. The DNA-HuAd5-MVA-Protein (DAMP) vaccine regimen induced a cellular response with a Th1 biased serum antibody response, alongside high serum and vaginal MOMP-specific antibodies. This regimen significantly enhanced clearance against intravaginal C. trachomatis serovar D infection in both BALB/c and B6C3F1 mouse strains. This enhanced clearance was shown to be CD4+ T cell dependent. Future studies will need to confirm the specificity and precise mechanisms of protection.

Conclusions: A C. trachomatis vaccine needs to induce a robust cellular response with broad cross-serovar coverage and that a heterologous prime-boost regimen may be an approach to achieve this.