Recombinant multi-epitope vaccine induce predefined epitope-specific antibodies against HIV-1.
Monoclonal antibody 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 has significant neutralization potency against 90% of the investigated viruses of African, Asia, American and European strains, but antibodies responses to ELDKWA-epitope in HIV-1 infected individuals were very low. Based on the epitope-vaccine strategy suggested by us, a recombinant glutathione S-transferase (GST) fusion protein (GST-MELDKWAGELDKWAGELDKWAVDIGPGRAFYGPGRAFYGPGRAFY) as vaccine antigen containing three repeats of neutralizing epitope ELDKWA on gp41 and GPGRAFY on gp120 was designed and expressed in Escherichia coli. After vaccination course, the recombinant multi-epitope vaccine could induce high levels of predefined multi-epitope-specific antibodies in mice. These antibodies in sera could bind to both neutralizing epitopes on gp41 peptide, V3 loop peptide and recombinant soluble gp41 (aa539-684) in ELISA assay (antisera dilution: 1:1,600-25,600), while normal sera did not. Moreover, these antibodies in sera could recognize the CHO-WT cells which expressed HIV-1 envelope glycoprotein on the cell surfaces, indicating that the predefined epitope-specific antibodies could recognize natural envelope protein of HIV-1 though these antibodies were induced by recombinant multi-epitope-vaccine. These experimental results suggested a possible way to develop recombinant multi-epitope vaccine inducing multi-antiviral activities against HIV-1.
Li
Hua
H
Laboratory of Immunology, Research Centre for Medical Science and Department of Biology, Tsinghua University, Protein Science Laboratory of the Ministry of Education, Beijing 100084, PR China.
Liu
Zu-Qiang
ZQ
Ding
Jian
J
Chen
Ying-Hua
YH
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D004926:Escherichia coli; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D019444:Vaccines, DNA / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins