Grant: CIHR Fellowship

A memory CD8 T cells is a type of white blood cell that remembers our body's exposure to a small portion of a pathogen called an antigen. These cells form the basis of vaccination and when they re-encounter the same pathogen or antigen, they respond by engaging our body's immune system to find and kill the invader. Most memory cells were thought to patrol our body and recirculate through the blood. Recently, however, a specialized type of memory T cell was discovered that resides in tissues including the genital tract, gut, lung, liver, etc. without recirculation. This specialized cell type is called a tissue-resident memory T cell (Trm) and is perhaps the most abundant T cell type in the body. The female genital tract is the most common portal of entry of HIV infections. In this project, we will test a novel vaccine that generates abundant CD8 Trm as well as antibodies that can target and kill a pathogen in the genital tract in mice. We will first test whether we can achieve abundant and highly functional CD8 Trm in the genital tract of rhesus macaques. We're using rhesus macaques as they are closely related to human beings and are a good model animal for HIV vaccine development. After vaccination is complete, we will test how well it functions within the animal by injecting SIV particle (monkey version of HIV) in the cervix as a model of HIV transmission. We expect our vaccine-generated CD8 Trm to respond to this SIV particle. We will thoroughly monitor many aspects of the immune response within the first two days after challenge as HIV is most vulnerable during this period. The response will be monitored not only throughout the genital tract, but also in blood, lymph nodes, and other tissues. The insights that we will gain from describing how CD8 Trm function after they 'see' antigen again may fundamentally alter our knowledge of their capacity and pave way for improved vaccine design against intractable diseases like HIV/AIDS, TB, malaria, and cancer.