Vaccine Virus Membrane Protein HLA Class II-Restricted T Cell Epitopes

Technology #2011-065

Three decades after the eradication of smallpox, the threat of bioterrorism and outbreaks of emerging diseases such as monkeypox have renewed interest in the development of safe and effective next-generation poxvirus vaccines and biodefense research. Current smallpox vaccines contain live virus and are contraindicated for a large percentage of the population. Safer, yet still effective inactivated and subunit vaccines are needed, and epitope identification is an essential step in the development of these subunit vaccines. In this study we focused on 4 vaccinia membrane proteins known to be targeted by humoral responses in vaccinees. In spite of the narrow focus of the study we identified 36T cell epitopes, and provide additional support for the physical linkage between T and B epitopes. This information may prove useful in peptide and protein-based subunit vaccine development as well as in the study of CD4 responses to poxviruses. As described herein, 36 viral epitopes were identified in vaccinia-virus membrane proteins B5R, L1R, A33R and A27L. Of the 36 epitopes identified, our results show that at least 19 of them were recognized by CD4T cells and are presented as HLA class II. The identification of these Vaccinia virus-derived membrane polypetides will aid in understanding the immune process and can be used in the generation of vaccines against the vaccinia virus. The polypeptides identified can be used in peptide vaccines, multivalent vaccines that contain HLA class I peptides as well as in kits used to detect cellular immune responses (antigen specific T cells), among others.