Identification of SARS-COV spike protein-derived and HLA-A2-restricted human CTL epitopes by using a new muramyl dipeptidederivative adjuvant.
Severe acute respiratory syndrome (SARS) spread during the winter of 2003, and attempts have been made to develop vaccines against SARS corona virus (SARS-CoV). The present study provides a strategy to rapidly identify SARS-CoV-derived antigenic peptides recognized by HLA-A2-restricted cytotoxic T lymphocytes (CTLs). Forty-three candidate peptides having HLA-A2-binding motifs were selected in silico and HLA-A2/Db chimeric MHC class I-transgenic mice were immunized with these peptides and a new derivative of muramyl dipeptide that can induce upregulation of HLA-DR, CD80, CD86, and CD40 in human CD14+ antigen presenting cells, was administered as an adjuvant. Six HLAA2-restricted mouse CTL epitopes were identified, including two new epitopes which have never been reported before. One of the novel peptides was naturally processed and successfully induced HLAA2-restricted specific CTLs in both HLA transgenic mice and healthy donors. The method was useful, convenient and efficient for rapid identification of CTL epitopes derived from SARS-CoV proteins and will be possibly applicable for other pathogens to develop a peptide-based vaccine.
Chen
Y-Z
YZ
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Liu
G
G
Senju
S
S
Wang
Q
Q
Irie
A
A
Haruta
M
M
Matsui
M
M
Yasui
F
F
Kohara
M
M
Nishimura
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064370:Spike Glycoprotein, Coronavirus; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine