HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies.
Some neutralizing epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro. But only very low levels of antibodies to these epitopes were determined in the HIV-1 infected individuals. In this study, the aluminum (alum) adjuvant to increase the immunogenicity of the neutralizing epitopes was used. Three epitope-peptides [C-(ELDKWAG)4, C-(RILAVERYLKD-G)2 and C-(GPGRAFY)2], which contain three epitopes (ELDKWA, RILAVERYLKD, GPGRAFY) from the HIV-1 Env proteins, were synthesized and conjugated to carrier protein keyhole limpet hemocyanin (KLH). The epitope-vaccines C-(ELDKWAG)4-KLH and C-(RILAVERYLKD-G)2-KLH in alum induced high levels of epitope-specific antibodies recognizing the epitopes from epitope-peptides C-(ELDKWAG)4 and C-(RILAVERYLKD-G)2, as well as the gp41 C-domain peptides P2 [C-TSLIHSLIEESQNQQEKNEQELLELDKWA (aa 646-674)] and P1 [LQARILAVERYLKDQQL (aa 583-599)] and the recombinant soluble gp41 (rsgp41) bearing both epitopes (antibody titer in rabbit sera was 1:12800-25,600 dilution). Immunoblotting analysis demonstrated that the antibodies in both antisera bound to rsgp41, indicating that both antibodies recognized the natural epitopes on rsgp41 protein. The epitope-vaccines C-(GPGRAFY)2-KLH induced moderate GPGRAFY epitope-specific antibody response with a titer of 1:6,400. In contrast, as it was demonstrated in previous studies, the immunization with rgp160 induced weak antibody response to these three epitopes (titer of 1:400-1600). This suggests that epitope-peptides conjugated to KLH when infected with alum significantly increases immunogenicity of gp41 neutralizing epitopes providing a hope for the development of an HIV-1 vaccine.
Tian
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Research Center for Medical Science and Department of Biological Science and Technology, Tsinghua University, Beijing, People's Republic of China.
Xiao
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Zhu
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Chen
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D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008969:Molecular Sequence Data; D011817:Rabbits
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C041524:aluminum sulfate