Finding the balance between protective and pathologic vaccine induced immunity using LCMV specific T lymphocytes

Abstract

Vaccination remains one of the most effective strategies for preventing human diseases caused by infectious pathogens, yet developing an efficacious vaccine for persistent viral infections such as HIV remains a difficult aim of much research. Vaccines expressing pathogen T cell epitopes has been a widely employed strategy to try and improve the efficacy of vaccines against chronic viral infections. However, selectively engaging T cells has the potential to increase rather than prevent pathology during subsequent infection, consequently shifting a mild disease to a lethal one. Thus, determining the immune parameters that lead to protection versus those that mediate pathology is critical for developing a safe and effective vaccine against persistent viral infections. Using lymphocytic choriomeningitis virus (LCMV) we investigated how the precursor frequency of CD8 T cells affects the balance of protection vs. pathology during chronic viral infection. We found that the balance is based largely on the number of T cells responding to the pathogen. Intermediate numbers of responding CD8 T cells resulted in maximum pathology. We have also observed that increasing vaccine-induced CD4 T cell responses, unlike CD8 T cells, never leads to protection, but instead high host mortality. We have now began to study the interaction of CD8 and CD4 T cells during infection to determine what effect CD4 T cells have in protective versus pathologic vaccine-induced immunity and what exactly mediates such responses.