๐ Efficient induction of cytotoxic T lymphocytes specific for severe acute respiratory syndrome (SARS)-associated coronavirus by immunization with surface-linked liposomal peptides derived from a non-structural polyprotein 1a
Spike and nucleocapsid are structural proteins of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) and major targets for cytotoxic T lymphocytes (CTLs). In contrast, non-structural proteins encoded by two-thirds of viral genome are poorly characterized for cell-mediated immunity. We previously demonstrated that nucleocapsid-derived peptides chemically coupled to the surface of liposomes effectively elicited SARS-CoV-specific CTLs in mice. Here, we attempted to identify HLA-A*0201-restricted CTL epitopes derived from a non-structural polyprotein 1a (pp1a) of SARS-CoV, and investigated whether liposomal peptides derived from pp1a were effective for CTL induction. Out of 30 peptides predicted on computational algorithms, nine peptides could significantly induce interferon gamma (IFN-ฮณ)-producing CD8+ T cells in mice. These peptides were coupled to the surface of liposomes, and inoculated into mice. Six liposomal peptides effectively induced IFN-ฮณ-producing CD8+ T cells and seven liposomal peptides including the six peptides primed CTLs showing in vivo killing activities. Further, CTLs induced by the seven liposomal peptides lysed an HLA-A*0201 positive cell line expressing naturally processed, pp1a-derived peptides. Of note, one of the liposomal peptides induced high numbers of long-lasting memory CTLs. These data suggest that surface-linked liposomal peptides derived from pp1a might offer an efficient CTL-based vaccine against SARS.
keywords
๐ severe acute (1373)
๐ viral genome (96)
๐ structural proteins (197)
๐ data suggest (146)
๐ respiratory syndrome (2004)
๐ acute respiratory (1734)
๐ cell line (211)
author
๐ค Kohyama, Shunsuke
๐ค Ohno, Satoshi
๐ค Suda, Tatsuya
๐ค Taneichi, Maiko
๐ค Yokoyama, Shoichi
๐ค Mori, Masahito
๐ค Kobayashi, Akiharu
๐ค Hayashi, Hidenori
๐ค Uchida, Tetsuya
๐ค Matsui, Masanori
year
โฐ 2009
journal
๐ Antiviral Research
issn
๐ 01663542 18729096
volume
84
number
2
page
168-177
citedbycount
6
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