Current influenza vaccines provide focused antibody-mediated protection against seasonal influenza strains included in the vaccine. However, they do not protect from co-circulating mismatched strains, and, more importantly, fail to provide protection against antigenic shifts that can cause potentially devastating pandemics. This proposal investigates the role of T cell immunity, on both the individual and population levels, in providing broad protection against diverse influenza strains. Animal and human studies showed that T cells can provide strain-transcending protection, resulting in more rapid viral clearance, decreased immunopathology, and improved clinical outcomes, and thus the improvement of strategies to induce protective levels of influenza- specific T cells are of critical importance. However, little is known about the rules for boosting influenza-specific resident memory T cells in the respiratory tract in the face of pre-existing humoral immunity from prior influenza infections or vaccinations. We will use multi-scale immuno-epidemiological methods that link the scales from the dynamics of infection and immunity within individuals to take of vaccination in the face of pre-existing immunity and the spread of infection on the population level. The knowledge gained form this study will help guide future vaccination efforts against influenza viruses to better generate broadly protective T cell immunity within individuals and across the population.
The effectiveness of T cell-based immunizations, such as with live attenuated influenza vaccines (LAIV), can be impacted by pre-existing immunity from prior vaccinations or natural infections. Determining the effectiveness of a T cell vaccine will thus require taking these factors into account, and this can only be done by multi-scale models integrating within-host and epidemiological scales. In this proposal we will determine epidemiological parameters from the experimentally validated within-host models and subsequently use the epidemiological models to examine how interference from pre-existing immunity can alter the efficacy of a T cell-based vaccine at the epidemiological level.
