[An investigation of the effect of H3-H3 peptide vaccine for preventing influenza virus infection in DQ6 mice]

Abstract

Based on the cassette theory that a core region of an immunogenic peptide is partially replaced with peptide fragments from various pathogens without any detrimental effects to their anchoring to the particular MHC class II molecules, we had prepared a peptide vaccine, 46F/HA127-133/54A (18mer) (YEGFS WTGVTQN KAKGIT), against A/Aichi/2/68 (H3N2) influenza viruses. It was shown that the 46F/HA127-133/54A (18mer) was effective in Ab mice. In the present study, we first examined whether this peptide vaccine could induce neutralizing antibodies against other H3 subtype influenza viruses. The results suggested that 46F/HA127-133/54A (18mer) would be effective for preventing infection with almost all H3 subtype influenza viruses. Since it has been demonstrated that the Ab binding component possesses a supermotif for binding to various MHC class II including HLA-DQ6, we next examined whether the peptide vaccines could be applicable to human positive of HLA-DQ6 type, using DQ6 mice that carry DQ6 alone as MHC class II molecules. The DQ6 mice had been prepared by crossing DQ6 transgenic mouse with murine class II knock out mouse and were thus regarded as a model of DQ6 positive individuals. In this particular experiment another peptide vaccine, H3-H3, which was newly prepared by adding HA127-133 to the C-terminus of 46F/HA127-133/54A (18mer) was used. It was demonstrated that the H3-H3 generated significant immunological responses and prevented infection with A/Aichi/2/68 viruses in the DQ6 mice. Altogether, it is suggested that the peptide vaccine, H3-H3, can be applicable to human positive of HLA-DQ6 type.