HIV and malaria are two of the most devastating infectious diseases in the world. In 2015, these diseases together caused over 1.4 million deaths. Although advances have been made in preventing new infections of both HIV and malaria, the risk of infection with either disease in the world's poorest nations is still great. Furthermore, as HIV and malaria are endemic to similar geographical areas, this overlap constitutes great risk for co-infection of individuals, which could fuel the spread of both diseases. Moreover, HIV and malaria infection have been shown to cause similar gastrointestinal pathologies, including disruption of the epithelial barrier and altered intestinal immune function. As infection across the rectal mucosa constitutes a major route for sexual transmission of HIV, it is possible that prior infection with malaria could increase the risk of acquisition of HIV, should exposure of this mucosal membrane occur. Importantly, as the biomedical research field moves closer to the development of an effective vaccine to prevent new HIV infections, it will be critical to take into account alterations in mucosal phenotype and function that may occur due to malaria infection, as these changes could impact the efficacy of the HIV vaccine. Here, we aim to determine how concurrent malaria infection could alter the efficacy of SHIV vaccination in rhesus macaques. We will assess immunological and microbial alterations in the intestinal mucosa during malaria infection and track these changes throughout subsequent SHIV vaccination and SHIV challenge, in order to elucidate how malaria may alter HIV vaccine responses and thus diminish protection from SHIV infection. These studies will generate critical knowledge of the impact of malaria on HIV vaccination strategies, which will aid in the development of vaccines that take into account environmental factors such as other co-endemic infectious diseases, and thus be effectively employed in the developing world, where the need for an HIV vaccine is the greatest.
Here, we propose to determine the impact of prior malaria infection on the efficacy of a novel mucosal SHIV vaccination strategy in non-human primates. We hypothesize that malaria infection will alter components of the gastrointestinal immune system, including the intestinal microbiome. These alterations will decrease the effectiveness of SHIV vaccination and increase the rate of SHIV acquisition after challenge.