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

• Published in: Vaccine 1999-03, Vol.17 (9), p.1161-1168
• Main Authors: Matsuki, Naoto, Ogasawara, Kazumasa, Takami, Kimitaka, Namba, Kenichi, Takahashi, Akio, Fukui, Yoshinori, Sasazuki, Takehiko, Iwabuchi, Kazuya, Good, Robert A, Onoé, Kazunori
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Genes, MHC Class II; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; Humans; Influenza A virus - genetics; Influenza A virus - immunology; Influenza Vaccines - chemical synthesis; Influenza Vaccines - immunology; Influenza virus; Influenza, Human - prevention & control; MHC; Mice; Mice, Mutant Strains; Microbiology; Molecular Sequence Data; Peptide vaccine; Peptides - chemical synthesis; Peptides - immunology; T-Lymphocytes - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(98)00336-3

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-2A b binding component induced significant T cell responses and antibodies (Ab) specific for HA127–133 in H-2A b mice. Further we found that the H-2A b 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.