Grant: Catalyst Grant: STBBI Research in Canada: Beyond HIV/AIDS/Hepatitis C - General

Chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in Canada, occurring in 346 in every 100,000 people. While the majority of infected individuals have no symptoms, untreated chlamydia in women can lead to pelvic inflammatory disease (PID), infertility and ectopic pregnancies. Although testing and treatment are available, the increasing prevalence of chlamydia in the population motivates the development of a vaccine. A recent human clinical trial for a protein chlamydia vaccine showed a good safety profile and immune responses in humans, but the vaccine immunization schedule requires five doses, which makes implementation challenging. Furthermore, the vaccines tested in animal models to-date do not completely prevent infection. We propose to test three types of chlamydia vaccines to identify how well they work for preventing infection, including a protein vaccine (similar to the one used in the human clinical trial), a messenger RNA vaccine (similar to the approved COVID-19 vaccines) and a self-amplifying RNA (saRNA) vaccine. Self-amplifying RNA is a type of messenger RNA that is able to replicate itself in a patient's cells, which increases the total amount and duration of the vaccine protein expression. We hypothesize that using self-amplifying RNA will allow us to use a lower dose of RNA than mRNA and fewer doses compared to the state-of-the protein chlamydia vaccine. We will characterize the immune responses with the protein, mRNA and saRNA vaccines and determine how well each of them protects against chlamydia infection. The results of this research will inform the design of future chlamydia vaccine candidates and seed a collaboration with the goal of developing and rolling out an effective chlamydia vaccine. Furthermore, the knowledge regarding the immune mechanisms of protein, mRNA and saRNA vaccines generated from these studies may be useful for development of vaccines against other STIs or infectious diseases.