Investigation of Chlamydia trachomatis PmpD and OmcB proteins as candidate vaccine immunogens and adhesins using structural and in vivo (360G-Wellcome-097325_Z_11_A)

Chlamydia trachomatis, an obligate intracellular bacterium, is the leading cause of preventable blindness worldwide, affecting between 300-500 million people, and is also the most common sexually transmitted disease with over 90 million new cases reported annually. Development of a vaccine has not been prioritized, probably due to the availability of antibiotics to treat the disease, difficulties in culture and genetic manipulation, and a limited understanding of the factors involved in host cell binding. The project aims to investigate two proteins as candidate vaccine immunogens, which are also implicated in chlamydial epithelial cell attachment - polymorphic membrane protein D (PmpD) and outer membrane complex B protein (OmcB). Initially, expression, purification and structure determination of the proteins will be carried out using X-ray crystallography to elucidate the nature of potential antigenic fragments. These in vitro and in silico approaches will be complemented by in vivo studies on C57BL/6 mice using identified recombinant PmpD and OmcB subunits as vaccine immunogens. Co-crystallisation experiments with PmpD and OmcB recombinant proteins and their putative ligands will be carried out to elucidate binding mechanisms that may facilitate the design of novel blocking agents and inhibitors.