SARS CTL Vaccine Candidates — HLA Supertype, Genome‐Wide Scanning and Biochemical Validation

Abstract

An effective SARS vaccine is likely to include components that can induce specific cytotoxic T‐cell (CTL) responses. The specificities of such responses are governed by HLA‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information. The latter was recently established when a causative coronavirus (SARS CoV) was isolated and full‐length sequenced. Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype, genome‐wide scan for SARS‐specific cytotoxic T cell epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all major human populations. For each HLA supertype, we have selected the 15 top candidates for test in biochemical‐binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.