Project Number: 3022-32000-025-008-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2021
End Date: Aug 31, 2026
The objective of this agreement is to evaluate mammalian host cellular immune responses to arboviral infections in order to better understand virus maintenance and transmission in United States (U.S.) livestock, with the aim of developing new countermeasures. Specific objectives include: 1) evaluate the role of T-cell responses in host protection against arboviral infections, and 2) use this information to develop new vaccine strategies. These efforts will provide new knowledge regarding arbovirus-mammalian host interactions and identify viral proteins needed for the development of diagnostic assays and contemporary vaccines.
This agreement combines expertise in arboviruses, flaviviruses, swine immunology, T-cell biology, and vaccine development to advance the mutual goal of understanding the host adaptive immune responses to arboviral infections and development of new countermeasures to prevent and control disease. First, swine T-cell responses, especially cytotoxic T lymphocytes (CTLs), will be studied to determine cell-mediated immune correlates of protection against Japanese encephalitis virus (JEV) infection. Whole viral antigens and CTL epitopes associated with protective responses will be identified and characterized. The empirically identified target antigens will then be used to generate DIVA compatible subunit vaccine candidates. Briefly, the approach will entail generation of CTLs, which will be validated for their ability to kill JEV-infected autologous antigen-presenting cells. The CTLs will then be used to down select vaccine candidate antigens and the defined CTL targets will be used to develop live-vectored antigen expression constructs that will be authenticated using the JEV-specific CTLs as above. The recombinant subunit vaccine candidates will be tested for safety, immunogenicity, and protective efficacy in commercial pigs. The JEV antigens will also be screened using convalescent sera to identify suitable diagnostic target(s) to allow development of a DIVA compatible subunit vaccine candidate.