Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope.

Abstract

The severe acute respiratory syndrome coronavirus nucleocapsid protein (SARS-CoV N) is one of the major targets for SARS vaccine due to its high potency in triggering immune responses. In this study, we have identified a novel HLA-A*0201 restricted epitope, N220 (LALLLLDRL), of the SARS-CoV N-protein through bioinformatics analysis. The N-protein peptide N220 shows a high binding affinity towards human MHC class I in T2-cells, and is capable of activating cytotoxic T-cells in human peripheral blood mononuclear cells (PBMCs). The application of using the N220 peptide sequence with a single-chain-trimer (SCT) approach to produce a potential DNA vaccine candidate was investigated in HLA-A2.1K(b) transgenic mice. Cytotoxicity assay clearly showed that the T-cells obtained from the vaccinated animals were able to kill the N-protein expressing cells with a cytotoxicity level of 86% in an effector cells/target cells ratio of 81:1 one week after the last vaccination, which is significantly higher than other N-protein peptides previously described. The novel immunogenic N-protein peptide revealed in the present study provides valuable information for therapeutic SARS vaccine design.

• Authors: Ying-Kit Cheung, Samuel Chak-Sum Cheng, Fion Wan-Yee Sin, Kin-Tak Chan, Yong Xie
• Journal: Vaccine (Vaccine) Vol. 25 Issue 32 Pg. 6070-7 (Aug 10 2007) ISSN: 0264-410X [Print] Netherlands
• PMID: 17629360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coronavirus Nucleocapsid Proteins
• Epitopes, T-Lymphocyte
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Nucleocapsid Proteins
• Vaccines, DNA
• Viral Vaccines

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cell Line
• Coronavirus Nucleocapsid Proteins
• Epitopes, T-Lymphocyte (immunology)
• HLA-A Antigens (immunology)
• HLA-A2 Antigen
• Humans
• Mice
• Mice, Transgenic
• Nucleocapsid Proteins (immunology)
• Severe acute respiratory syndrome-related coronavirus (immunology)
• Severe Acute Respiratory Syndrome (immunology)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccines, DNA (immunology)
• Viral Vaccines (immunology)