Investigating Immunogenicity of Mpox and Mpox vaccine Imvamune in people living with HIV

Mpox is a disease caused by a poxvirus of the same name. It is predominantly transmitted from wild animals to humans in Central and West Africa. It occurs rarely outside Africa. However, starting May 2022, Mpox outbreaks occurred in many non-African countries in the World including Canada. Quite surprisingly, the disease was not only transmitted from humans to humans but also sexually. In these outbreaks, a very high percentage of people living with HIV (PLWH) as well as men having sex with men (MSM) were infected (up to 51% of cases) suggesting that PLWH and MSM are more vulnerable to the disease. Canada has a large population (> 63000) of PLWH. A poxvirus vaccine, Imvamune, has been approved in Canada for protection from Mpox. PLWH and MSM are vaccinated with this vaccine. Although antiretroviral therapy suppresses HIV replication in PLWH, it does not fully restore immune function. Therefore, the immunogenicity of the Mpox vaccine in PLWH and MSM remains unknown. In simpler words we need to know ability of PLWH to generate antibodies and T cells that protect them from a future Mpox. The present research project is aimed to address this question. It is noteworthy that Imvamune vaccine is based upon a whole live virus. Some of the viral proteins are not relevant to vaccine and may be unsafe for people like PLWH. In this research proposal, we aim to identify T cell epitopes (small fragments of proteins derived from immunity-generating viral proteins), which could enable development of high tech mRNA-based vaccines for Mpox. An additional issue that our research proposal will address is "how has Mpox evolved to become more efficient in human to human spread and become a sexually transmitted disease?" Using state of the art technology of sequencing and bioinformatics tools, we hope to find answer to this question. Overall, the results from this project will make Canada better prepared to protect vulnerable populations from future Mpox outbreaks.