A STRATEGY FOR MAKING SYNTHETIC PEPTIDE VACCINES

被引:31
作者
OGASAWARA, K
NARUSE, H
ITOH, Y
GOTOHDA, T
ARIKAWA, J
KIDA, H
GOOD, RA
ONOE, K
机构
[1] HOKKAIDO UNIV,FAC VET MED,INST IMMUNOL SCI & VET HYG & MICROBIOL,ANIM EXPTL LAB,SAPPORO,HOKKAIDO 060,JAPAN
[2] UNIV S FLORIDA,ALL CHILDRENS HOSP,ST PETERSBURG,FL 33701
关键词
INFLUENZA VIRUS; HELPER T-CELL; NEUTRALIZING ANTIBODY; AGRETOPE;
D O I
10.1073/pnas.89.19.8995
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have determined the H-2 class II allele-specific amino acid motif of the agretope (the site of contact between the peptide antigen and the major histocompatibility complex) for a synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58). Residues 46 and 54 functioned as the agretope, and residues 50 and 52 functioned as the epitope (the site for contact between the peptide antigen and the T-cell antigen receptor). In general, agretopes and epitopes function independently. Thus, substitution of amino acids in the epitope does not significantly affect binding of the peptide antigen to a class II molecule. On the basis of these findings, synthetic peptide vaccines against influenza Aichi (H3N2) virus were prepared by introducing seven residues of the influenza virus hemagglutinin into the frame component residues 43-46 and 54-58 of p43-58 analogues including the agretopes for A(k) or A(b) previously determined on the p43-58 segment. These peptide vaccines induced both helper T-cell responses and production of antibodies that were specific for influenza Aichi hemagglutinin but not for the major histocompatibility complex binding frame in mice bearing A(k) or A(b). The antibodies produced neutralize the infectivity of influenza Aichi in vitro. The present findings should provide a basis for preparing potent peptide vaccines that function without producing side effects.
引用
收藏
页码:8995 / 8999
页数:5
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