Courtesy Leah Hohman
Oct. 13, 2021
Recent study by Snyder Institute researchers shows significant implications for vaccine strategies against infections
Many infectious diseases for which we do not have effective vaccines require the generation of cell mediated immunity orchestrated by T cells of the adaptive immune system. These infections are typically intracellular, whereby a pathogen establishes a permissive niche within cells of the body. Vaccination against these pathogens has often failed, despite the ability of many experimental vaccines to generate memory T cells.
Recently, investigators at the Snyder Institute for Chronic Diseases have discovered why this may be. PhD graduate Leah Hohman in the lab of Snyder member Nathan Peters (https://www.nathanpeterslab.ca/) found that effective T cell mediated immunity must pre-exist the establishment of the pathogen niche.
T cells that were highly protective if present at the time of infection completely lost their protective capacity if provided after niche establishment due to the genetic and functional reprogramming of host cells by a pathogen. Therefore, the present lack of effective T cell-mediated vaccines that target memory T cell generation may be because protective immunity relies on pre-activated cells and availability prior to the establishment of a pathogen niche, which occurs before memory T cells acquire effector function.
These observations are the first to formally demonstrate the degree to which T cells are reliant on the time at which they interact with infected cells to mediate protection. The findings, published in PLOS Pathogens, have significant implications for vaccine strategies against infections such as Leishmania spp., Mycobacterium tuberculosis, Salmonella enterica, and Crytococcus spp.