Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory

Naoto Matsuki, Kazumasa Ogasawara, Kimitaka Takami, Kenichi Namba, Akio Takahashi, Yoshinori Fukui, Takehiko Sasazuki, Kazuya Iwabuchi, Robert A. Good, Kazunori Onoé

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Abstract

We proposed a strategy (cassette theory) in which non-binding peptides for murine major histocompatibility complex (MHC) class II molecules are introduced into a MHC-binding component to render the resultant hybrid peptides bound to the MHC and thus immunogenic in animals carrying the relevant MHC. It was shown that 46F/HA127-133/54A(18mer) peptide which was prepared by introducing hemagglutinin (HA)127-133 of influenza virus into the H-2Ab binding component induced significant T cell responses and antibodies (Ab) specific for HA127-133 in H-2Ab mice. Further we found that the H-2Ab binding component had a supermotif for human class II molecules (i.e. HLA- DQ6). In the present study, a new peptide vaccine, H3-H3, was prepared by combining 46F/HA127-133/54A(18mer) as a carrier and HA127-133 attached to the C terminus of 46F/HA127-133/54A(18mer) as a hapten and the effect of vaccine was examined in DQ6 mice which carry HLA-DQ6 alone as MHC class II molecules and thus may be regarded as a model of the DQ6 positive individuals. Since 46F/HA127-133/54A(18mer) induced merely Ab against HA127-133, it was assumed that H3-H3 induced mainly HA127-133 specific Ab in DQ6 mice without undesirable Ab production against the carrier. Indeed, H3-H3 elicited T cell responses and induced HA127-133 specific Ab in DQ6 mice. Furthermore, administration of H3-H3 inhibited growth of influenza virus until 9 weeks after the last immunization in DQ6 mice.

Original languageEnglish
Pages (from-to)1161-1168
Number of pages8
JournalVaccine
Volume17
Issue number9-10
DOIs
Publication statusPublished - Mar 5 1999

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Matsuki, N., Ogasawara, K., Takami, K., Namba, K., Takahashi, A., Fukui, Y., Sasazuki, T., Iwabuchi, K., Good, R. A., & Onoé, K. (1999). Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory. Vaccine, 17(9-10), 1161-1168. https://doi.org/10.1016/S0264-410X(98)00336-3