Identification of a DRB3*011:01-restricted CD4+ T cell response against bovine respiratory syncytial virus fusion protein

Authors: Kaplan, Bryan; HOFSTETTER, AMELIA - National Institutes Of Health (NIH); MCGILL, JODI - Iowa State University; Lippolis, John; NORIMINE, JUNZO - University Of Miyazaki; Dassanayake, Rohana; Sacco, Randy

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2023
Publication Date: 2/20/2023
Citation: Kaplan, B.S., Hofstetter, A.R., McGill, J.L., Lippolis, J.D., Norimine, J., Dassanayake, R.P., Sacco, R.E. 2023. Identification of a DRB3*011:01-restricted CD4+ T cell response against bovine respiratory syncytial virus fusion protein. Frontiers in Immunology. 14. Article 1040075.. https://doi.org/10.3389/fimmu.2023.1040075.
DOI: https://doi.org/10.3389/fimmu.2023.1040075

Interpretive Summary: Human respiratory syncytial virus (HRSV) infects nearly every child by two years of age and subsequent reinfections can occur later in life. No safe, effective vaccines have been developed for HRSV. Bovine respiratory syncytial virus (BRSV) is a related virus of cattle that is highly similar to HRSV and, like HRSV causes significant respiratory disease in calves making BRSV an attractive model for vaccine development to both BRSV and HRSV. To better understand the immune response to BRSV infection we assessed the T cell responses in cows with a history of annual vaccinations. Following stimulation with synthetic peptides derived from the BRSV F protein sequence, T cells from cows with the major histocompatibility complex class II allele DRB3*011:01 responded strongly to peptides containing the amino acid sequence INDMPITND, thus identifying a novel T cell epitope and defining the minimum peptide sequence. This information will aid in vaccine development.

Technical Abstract: No safe, reliable vaccines have been developed for respiratory syncytial virus (RSV). Although killed-virus vaccines are available for the closely related bovine RSV (BRSV), their efficacy is controversial. BRSV infection of calves is an attractive model of RSV infection. There is significant homology between BRSV and RSV, complimented by similar natural infection disease course and symptoms. A better understanding of the immune response elicited by BRSV vaccines will aid both BRSV vaccine improvement and RSV vaccine development. We screened for BRSV-specific T cell responses in cows with a history of annual vaccinations. We defined the minimum BRSV F peptide 261-269 (INDMPITND), which elicits IFN-' from CD4 T cells in five of fourteen cows tested. The response is restricted by the bovine class II MHC molecule DRB3. All five cows share the DRB3*1101 allele. We are currently developing a specific DRB3*1101:INDMPITNDQ tetramer to facilitate further characterization of this response.