Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory.
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.
Matsuki
N
N
Section of Pathology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Ogasawara
K
K
Takami
K
K
Namba
K
K
Takahashi
A
A
Fukui
Y
Y
Sasazuki
T
T
Iwabuchi
K
K
Good
R A
RA
Onoé
K
K
D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000138:chemical synthesis / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D010455:Peptides; D014614:Vaccines, Synthetic