[Development of synthetic peptide vaccine against influenza--T cell epitope the hemagglutinin of A/Aichi/2/68(H3N2) influenza virus induced immune response in mice].
Residues 46 and 54 of a synthetic peptide composed of residues 43-58 (AEGFSYTDANKNKGIT) of pigeon cytochrome c (p43-58) function as the agretope (the site of contact between the major histocompatibility complex and the antigen) and residues 50 and 52 function as the epitope (the site of contact between the T cell receptor and the peptide antigen). 46F54A peptide which was prepared by reserving phenylalanine (F) at an agretopic position 46 but substituting asparagine (N) to alanine (A) at the other agretopic position 54 bound to I-Ab molecule more tightly than p43-58. Previously, it was demonstrated that F at position 46 and A at position 54 functioned as the agretope in the 46F54A-specific and I-Ab-restricted T cell responses. Then I proved that these substitutions of amino acids at the agretopic positions did not affect the epitopic function, and substitutions of amino acids at the epitopic positions did not affect the binding between the agretope and MHC class II molecule each other. In the present study, I synthesized peptide vaccine by introducing several peptide fragments deduced from the hemagglutinin (HA) of A/Aichi/2/68 (H3N2) influenza virus into the central epitopic part of 46F54A. 46F/HA127-133/54A (18mer) which was synthesized by substituting residues 48-52 of 46F54A to residues 127-133 of the HA could induce antigen specific proliferative response of T cells in I-Ab mice. In the sera obtained from the I-Ab mice immunized intraperitoneally with 46F/HA127-133/54A (18mer) specific antibodies to A/Aichi/2/68 (H3N2) influenza virus were detected by ELISA. In addition, the sera neutralized infectivity of the virus in plaque reduction test using MDCK cells in vitro. This synthetic peptide vaccine was incorporated in multi-lamella-liposome and administered intranasally to I-Ab mice. The mice were protected from challenge infection with A/Aichi/2/68 (H3N2) influenza virus in vivo.
Naruse
H
H
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D000939:Epitopes; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000939:Epitopes; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic