Grant: Op. Gr.: STBBI Research in Canada: Beyond HIV/AIDS and Hepatitis C - Chlamydia

Chlamydia trachomatis (C.t.) is a leading bacterial causal agent of sexually transmitted and blood-borne infections (STBBIs), responsible for approximately 130 million cases annually. The C.t. infection is often asymptomatic but if left untreated, chlamydia infection can lead to serious complications, such as infertility, fatal ectopic pregnancy, and pelvic inflammatory diseases in females. Therefore, the development of a vaccine against Chlamydia is an international priority. Unfortunately, the diverse population of different serovars of C.t. responsible for urogenital infection makes vaccine development challenging. The C.t. major outer membrane protein (MOMP) has been identified as the most efficient target for C.t. vaccine development. However, the structure of MOMP is complex, and refolding a recombinant construct into the correct native conformation is technically difficult. So, the more close attention has shifted to selected regions, such as the variable domain 1 (VD1) and VD4 in MOMP which were able to induce neutralizing antibodies against C.t. infection. Thus, this study aims to use our new dendritic cell (DC)-targeting technology to present multiple copies of VD1 and VD4 from different urogenital C.t. serovars to develop a vaccine that could induce robust and broad immune responses against different C.t. urogenital infections. Furthermore, these newly generated immunogens will be expressed in an efficient vesicular stomatitis virus (rVSV) vaccine vector and test its efficacy to protect from C.t. urogenital infections. We believe that the success of this study will provide proof of the principle that enhancement of DC targeting and the immunogenicity of the multiple copies of C.t. MOMP VD1/VD4 regions could induce protective immunity against various C.t. serovars. Overall, the demonstration of the efficacy of these VSV-based VD1/VD4 vaccine approaches may open new avenues for an effective prophylactic vaccine against C.t. urogenital infection.