Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection.

Abstract

Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost. Compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide (RBD-Pep) boost induced similar levels of Th1 and neutralizing antibody responses that protected the vaccinated mice from subsequent SARS-CoV challenge, but stronger Th2 and CTL responses. No significant immune responses and protective effects were detected in mice vaccinated with RBD-Pep or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, which may be effective against viruses with mutations in the neutralizing epitopes, our results suggest that the vaccination protocol used may be ideal for providing effective, broad and long-term protection against SARS-CoV infection.

• Authors: Lanying Du, Guangyu Zhao, Yongping Lin, Chris Chan, Yuxian He, Shibo Jiang, Changyou Wu, Dong-Yan Jin, Kwok-Yung Yuen, Yusen Zhou, Bo-Jian Zheng
• Journal: Vaccine (Vaccine) Vol. 26 Issue 13 Pg. 1644-51 (Mar 20 2008) ISSN: 0264-410X [Print] Netherlands
• PMID: 18289745 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Coronavirus M Proteins
• Epitopes
• Immunoglobulin G
• M protein, SARS-CoV
• Receptors, Virus
• Vaccines, Synthetic
• Viral Matrix Proteins
• Viral Vaccines

Topics

• Animals
• Antibody Formation (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Coronavirus M Proteins
• Dependovirus (genetics, immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes (immunology)
• Female
• Flow Cytometry
• Immunity, Cellular (immunology)
• Immunization Schedule
• Immunization, Secondary
• Immunoglobulin G (analysis, biosynthesis)
• Mice
• Mice, Inbred BALB C
• Neutralization Tests
• Receptors, Virus (genetics, immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Severe acute respiratory syndrome-related coronavirus (immunology)
• Severe Acute Respiratory Syndrome (immunology, prevention & control, virology)
• T-Lymphocytes (immunology)
• Vaccines, Synthetic (immunology)
• Viral Matrix Proteins (genetics, immunology)
• Viral Vaccines (immunology)