Novel bioparticle vaccines against Chlamydia trachomatis

Chlamydia trachomatis, a sexually transmitted obligate intracellular bacterium, presents a significant global public health concern due to its high prevalence. Although C. trachomatis infection often remains undetected, it can lead to serious complications such as pelvic inflammatory disease, infertility, ectopic pregnancy, miscarriage, and even blindness. While antibiotics are effective against acute infection, they are believed to increase the risk of reinfection. Despite advances in understanding C. trachomatis-caused infectious diseases, a prophylactic vaccine against the bacterium is yet to be developed. The challenges lie in the safety risks associated with using weakened live vaccines and the limited efficacy of current alternative vaccination strategies. Protective immunity against C. trachomatis, like other intracellular pathogens, relies on both humoral and cellular immune responses, targeting the extracellular and intracellular stages of the bacterium, respectively. Many studies have focused on inducing protective CD4+ (Th1) T cell-mediated and humoral responses, but efforts to activate CD8+ T cells, responsible for monitoring and eliminating intracellular infections, are still in the early stages. Therefore, the development of innovative C. trachomatis vaccines, capable of inducing potent humoral and cellular (CD4+ and CD8+ T cell) responses, requires a complementary interdisciplinary approach with experts from various fields. The main objective of this thesis was to create and evaluate novel C. trachomatis bioparticle vaccines, using bacterial outer membrane vesicles (OMVs) and protein bodies (PBs) as delivery platforms. Several vaccine candidates based on LPS-detoxified Salmonella OMVs and E. coli PBs have been generated. Preclinical testing in a mouse model has shown that the OMV/PB-based vaccines are safe and immunogenic, inducing specific humoral and cellular immune responses against C. trachomatis antigens in both systemic and mucosal compartments. Currently, the protective efficacy of the most promising vaccine is being evaluated and compared to other vectored vaccines using a genital mouse challenge model.