Immunogenicity of neutralizing epitopes on multiple-epitope vaccines against HIV-1.
Based on our hypothesis that epitope vaccine may be a new strategy to induce high levels of neutralization antibodies against HIV-1, we prepared multiple-epitope vaccines using three neutralizing epitopes (GPGRAFY, RILAVERYLKD and ELDKWA) of HIV-1 gp160, and characterized their immunogenicity. Peptide 1 [C-G-(ELDKWA-GPGRAFY)(2)-K] and peptide 2 (CG-GPGRAFY-ELDKWA-G-RILAVERYLKD) were synthesized and conjugated with carrier protein bovine serum albumin (BSA). After vaccination antibody responses to these immunogens were induced and evaluated by ELISA. The C-G-(ELDKWA-GPGRAFY)(2)-K-BSA (BSA: carrier protein) multiple-epitope vaccine induced a strong antibody response to the C-G-(ELDKWA-GPGRAFY)(2)-K peptide (antibody titer: 1:25,600) and C-(ELDKWAG)(4) peptide (antibody titer: 1:12,800), but a weak antibody response to the C-(GPCGRAFY)(4) peptide. The CG-GPGRAFY-ELDKWA-G-RILAVERYLKD-K-BSA (BSA: carrier protein) multiple-epitope vaccine also induced strong antibody response to the CG-GPGRAFY-ELDKWA-G-RILAVERYLKD-K peptide (antibody titer: 1:25, 600) and C-(ELLDKWAG)(4) peptide (antibody titer: 1:6,400), a very strong response to C-(RIVALVERYLKD-G)(2)-K peptide (dilution: 1:102, 400), and a very weak response to the C-(GPGRAFY)(4) peptide (dilution: 1:400) in mice. Both antisera induced by both multiple-epitope vaccines interacted with the recombinant soluble gp41 (rgp41), but did not bind two control peptides. In comparison with both epitope vaccines, the rgp160 subunit vaccine could induce weak epitope-specific antibody response to these three epitopes on the three epitope peptides and V3, N-domain and C-domain peptides (dilution: 1:400-1:1,600). These results indicate that both multiple-epitope vaccines could induce high levels of antibodies to both neutralizing epitopes RILAVERYLKD and ELDKWA, while the GPGRAFY epitope on both vaccines appeared to have weak immunogenicity. Both multiple-epitope vaccines showed significant potency on inducing high levels of epitope-specific neutralization antibodies in comparison with rgp160 subunit vaccine.
Lu
Y
Y
Laboratory of Immunology, Research Center of Medical Science and School of Life Science and Engineering, Tsinghua University, Beijing, PR China.
Xiao
Y
Y
Ding
J
J
Dierich
M
M
Chen
Y H
YH
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000032:analysis; D015488:HIV Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D010446:Peptide Fragments; D014614:Vaccines, Synthetic