Isaruliants M G, Ruden U, Wahren B
Department of Virology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Biokhimiia. 1996 Jul;61(7):1230-40.
Rabbits were immunized with a mixture of linear cojoined peptides (composites) combining an immunodominant B-cell epitope from gp41 of HIV-1 (amino acids 593-604) and a heterogeneous T-cell epitope from tetanus toxoid or hepatitis B core antigen. HIV-1 B-epitope in the context of the composites induced HIV-1 specific antibody response, while no antibodies were produced in response to the peptide representing single HIV-1 B-epitope. Competition ELISA and ELISA of HIV-1 peptide omission analogous demonstrated that immunization induced antibodies of the correct specificity. T-Cell epitopic components also elicited potent antibody production. T-Cell epitopes appeared to be immunodominant. However, HIV-1 specific antibody response was not suppressed, on the contrary, antibody response against HIV-1 B- and heterologous T-cell epitopes developed in parallel. Cellular responses against composite peptides and/or their components were induced in all animals. The ability to develop cellular response against T-cell epitopes from the composites determined the efficacy of humoral response against the composites including HIV-1 specific one. Animals with strong cellular responses rapidly developed maximum antipeptide antibody titers. The immunization results imply that colinear fusion of B- and T-cell epitopes yielded bivalent multiepitopic products in which the immunological properties of the individual components were maintained and desired immunogenic properties were obtained. Immunogenicity of the composite peptides corresponded to that expected from the study of the composite antigenic properties.
用线性连接肽(复合物)混合物对兔子进行免疫,该混合物结合了来自HIV-1 gp41的免疫显性B细胞表位(氨基酸593 - 604)和来自破伤风类毒素或乙肝核心抗原的异源T细胞表位。复合物中的HIV-1 B表位诱导了HIV-1特异性抗体反应,而针对单一HIV-1 B表位的肽未产生抗体。竞争ELISA和HIV-1肽缺失ELISA类似地表明免疫诱导了具有正确特异性的抗体。T细胞表位成分也引发了有效的抗体产生。T细胞表位似乎具有免疫显性。然而,HIV-1特异性抗体反应并未受到抑制,相反,针对HIV-1 B表位和异源T细胞表位的抗体反应并行发展。所有动物均诱导出针对复合肽和/或其成分的细胞反应。针对复合物中T细胞表位产生细胞反应的能力决定了针对包括HIV-1特异性反应在内的复合物的体液反应的效力。具有强烈细胞反应的动物迅速产生最大抗肽抗体滴度。免疫结果表明,B细胞和T细胞表位的共线性融合产生了二价多表位产物,其中各个成分的免疫特性得以保留,并获得了所需的免疫原性特性。复合肽的免疫原性与对复合抗原特性研究预期的结果一致。