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 introd uced into a MHC-binding component to render the resultant hybrid peptides b ound 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 in troducing hemagglutinin (HA)127-133 of influenza virus into the H-2A(b) bin ding component induced significant T cell responses and antibodies (Ab) spe cific for HA127-133 in H-2A(b) mice. Further we found that the H-2A(b) bind ing 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 combin ing 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 molecule s and thus may be regarded as a model of the DQ6 positive individuals. Sinc e 46F/HA127-133/54A(18mer) induced merely Ab against HA127-133, it was assu med that H3-H3 induced mainly HA127-133 specific Ab in DQ6 mice without und esirable Ab production against the carrier. Indeed, H3-H3 elicited T cell r esponses and induced HA127-133 specific Ab in DQ6 mice. Furthermore, admini stration of H3-H3 inhibited growth of influenza virus until 9 weeks after t he last immunization in DQ6 mice. (C) 1999 Elsevier Science Ltd. All rights reserved.