[Induction of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice by peptide vaccines].

A non-immunogenic peptide in mice bearing a certain MHC molecule can be rendered immunogenic, when the peptide is introduced into an MHC-binding component (cassete theory). We applied the cassete theory to preparation of effective peptide vaccines. Indeed a 46F/HA127-133/54A peptide vaccine which had been prepared by introducing hemagglutinin (127-133) of influenza virus, A/Aich/2/68 (H3N2), into H-2Ab-binding component derived fom pigeon cytochrom c (43-58) induced significant immunological responses in H-2Ab mice. In the present study to examine whether the peptide vaccines are effective in human positive of HLA-DQ6 type, DQ6 mice were established as a model of HLA-DQ6 positive individuals by crossing HLA-DQ6 transgenic mice with murine class II knockout mice. It was shown that the DQ6 mice carried only HLA-DQ6 as MHC class II molecules. We then immunized these DQ6 mice with peptide vaccines, 46F/J2/54A or 46F/J2/54A/J2, which had been prepared by introducing B subtype consensus sequence (IGP-GRAF) of the HIV-1 V3 region (J2) into an MHC-binding component containing a supermotif for binding to various MHC class II molecules. An original V3 peptide including the consensus sequence was non-immunogenic in the DQ6 mice. In contrast, the both peptide vaccines induced significant T cell responses in the DQ6 mice. Antisera from DQ6 mice that had been immunized with the peptide vaccines neutralized not only laboratory B subtype strains but also several clinical isolates of E subtype strains of HIV-1 in vitro. From these findings, it is anticipated that these peptide vaccines may protect DQ6 positive individuals from infection with various HIV-1 variants.