Immunisation with recombinant polymorphic membrane protein D elicits robust protection against sexually transmitted Chlamydia trachomatis infection

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial pathogen worldwide, responsible for ~90 million new cases of disease each year, with asymptomatic infections giving rise to sequelae such as pelvic inflammatory disease, ectopic pregnancy and infertility in women. Aggressive ‘seek and treat’ public health measures have not stemmed the rise of Ct infections, leading to proposal of the ‘arrested immunity’ hypothesis, where herd immunity within a population is blunted following earlier treatment with antibiotics. This suggests vaccination as the next key step in potentially eliminating Ct infections. Due to the paucity of robust clinical data, protective immune parameters have largely been derived from studies in mice, where pathogen-specific Th1-type immunity involving CD4+ T cells has been the focus of preclinical vaccine development. Our study represents the first preclinical characterization of a novel, rationally designed second-generation lipid adjuvant (SLA) in combination with the highly conserved recombinant Ct polymorphic membrane protein D (rPmpD) antigen. We demonstrate robust protection against urogenital Ct infection in the C57BL/6 murine model, characterized by significantly enhanced resistance to infection and reduction in mean bacterial load. However, enhanced Th1-type immunity was not found to correlate with relative protection, which rather coincided with the presence of robust rPmpD-specific serum and cervico-vaginal IgG titres. Prior to our study, the only convincing evidence of neutralizing antibodies effecting protection against chlamydial infection in vivo has emerged from studies employing the antigenically variable Ct MOMP as a vaccine immunogen. We propose that anti-rPmpD antibodies may play a significant role in vaccine-induced protection against urogenital Ct challenge, and that the role of antibodies warrants further investigation in future Ct vaccine development.