Identification of epitope-specific T cell responses to Lassa by genome-wide antigen screening and conservation across Arenaviridae 4344

Abstract Description CD4 and CD8 T cells play a key role in clearing Arenaviridae infections, even before the appearance of neutralizing antibodies. Thus, while vaccine strategies that would generate a rapid and durable neutralizing antibody response are desirable, a vaccine also inducing a rapid and durable T cell response would be of significant interest, especially if the T cell response could broadly target different viral species and isolates. Studies performed on Lassa survivors also show a robust and durable T cell response able to cross-recognize different Lassa lineages. Human data is, however, limited, and most studies so far focused on specific domains or immunodominant epitopes for GPC and NP. We have initiated a systematic analysis of all Lassa proteins (including GPC, N, and L proteins), in terms of which epitopes are immunogenic in humans, using a de-novo in-vitro stimulation approach. This approach will also determine the degree of conservation of Lassa human epitopes in other viruses of the Arenaviridae family (Old World and New World arenaviruses alike). Our approach re-identified epitopes previously shown in convalescent Lassa human samples and greatly expanded the immunogenic regions induced by this virus in GPC, N, and L proteins and identified several immunogenic and conserved regions, thus allowing us to assess the feasibility of a pan-Arenaviridae vaccine approach. Funding Sources This study has been supported by the NIH/NIAID contract No.75N93024C00056 and the Coalition for Epidemic Preparedness Innovations (CEPI). Topic Categories Viral Immunology (VIR)