Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania Health System, and The Wistar Institute, Philadelphia, PA 19104, USA.
Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein
The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2(b)-restricted epitopes (S436-443 and S525-532) and one H-2(d)-restricted epitope (S366-374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.
Virology. 335(1): 34-45.
The goal of this study is to identify murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein. For this purpose, synthetic spike gene sequence was designed with human pattern of codon usage. C57BL/6 mice and BALB/c mice were immunized with vectors encoding wild type spike and codon- optimized spike to identify CD8 T-cell epitopes. Results showed that the vector encoding codon-optimized spike generated strong spike-specific CD8 T-cell responses.