Impact of Malaria Co-Infection on HIV Vaccination

摘要 艾滋病毒和疟疾是世界上两种最具破坏性的传染病。2015年，这些 这些疾病共造成140多万人死亡。尽管在预防新的 尽管艾滋病毒和疟疾的感染，在世界上最贫穷的国家感染这两种疾病的风险仍然很高， 太好了此外，由于艾滋病毒和疟疾在相似的地理区域流行， 个人合并感染的风险很大，这可能助长这两种疾病的传播。此外，艾滋病毒和 疟疾感染已被证明会引起类似的胃肠道病变，包括破坏胃肠道， 上皮屏障和肠免疫功能改变。由于直肠粘膜的感染构成了 作为艾滋病毒性传播的主要途径，先前感染疟疾可能会增加风险 在感染HIV的过程中，如果发生粘膜暴露。重要的是，作为生物医学 研究领域更接近于开发一种有效的疫苗，以防止新的艾滋病毒感染，它将是 考虑到疟疾可能导致的粘膜表型和功能的改变至关重要 这些变化可能会影响艾滋病毒疫苗的有效性。在这里，我们的目标是确定如何 并发疟疾感染可改变恒河猴中SHIV疫苗接种的效力。我们将评估 疟疾感染期间肠粘膜的免疫学和微生物改变，并跟踪这些变化。 在随后的SHIV疫苗接种和SHIV攻击过程中的变化，以阐明疟疾如何可能 改变HIV疫苗反应，从而减少对SHIV感染的保护。这些研究将产生 关于疟疾对艾滋病毒疫苗接种战略的影响的重要知识，这将有助于制定 考虑到环境因素的疫苗，如其他共同流行的传染病， 在发展中国家，艾滋病毒疫苗的需求是最大的。

ABSTRACT 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.