Xiao Y, Liao M, Lu Y, Dierich M P, Chen Y H
Laboratory of Immunology, Research Center for Medical Research and School of Life Science and Engineering, Tsinghua University, Beijing, PR, China.
Immunobiology. 2000 Jan;201(3-4):323-31. doi: 10.1016/S0171-2985(00)80087-X.
Based on the experimental evidence that gp120 subunit vaccine did not protect individuals from HIV-1 infection, we suggested that epitope-vaccines of HIV-1 gp41 may be a new strategy to induce high levels of neutralizing antibodies against HIV-1, and characterised immunogenicity of epitope-vaccines. Two epitopes, RILAVERYLKD-epitope (aa586-596) on the N-domain and ELDKWA-epitope (aa669-674) on the C-domain of gp41, were demonstrated by us and others to induce protective activity. After vaccination course, the RILAVERYLKD-dimer epitope-vaccine [C(RILAVERYLKDG)2-BSA] induced strong epitope-specific antibody response by about 1:25,600 dilution, and the ELDKWA-tetramer epitope-vaccine [C-(ELDKWAG)4-BSA] could yet induce strong antibody response to ELDKWA-epitope by 1:12,800-25,600 dilution of antisera in mice, while rgp41 subunit vaccine induced very weak antibody response to both epitopes (1:400). In rabbit experiments, the titres of ELDKWA-epitope-specific antibody induced by ELDKWA-epitope-vaccine [C-(ELDKWAG)4-BSA] reached to 1:6,400, while rgp41 subunit vaccine induced very weak antibody response to this epitope and to P1 and P2 peptides (1:400). Moreover, the ELDKWA-epitope-specific antibodies in mice and rabbit antisera induced by epitope-vaccine could very strongly interact with P2 peptide sequence-corresponding to the C-domain of gp41 (dilution by 1:25,600), and the RILAVERYLKD-epitope-specific antibodies in mice antisera induced by epitope-vaccine could also very strongly interact with P1 peptide sequence-corresponding to the N-domain of gp41 (dilution by 1:102,400). All these results provided experimental evidence that epitope-vaccine may be a new general strategy to induce high levels of neutralizing antibodies against HIV-1 or other viruses.
基于gp120亚单位疫苗不能保护个体免受HIV-1感染的实验证据，我们提出HIV-1 gp41表位疫苗可能是诱导高水平抗HIV-1中和抗体的一种新策略，并对表位疫苗的免疫原性进行了表征。我们和其他人已证明，gp41的N结构域上的RILAVERYLKD表位（氨基酸586 - 596）和C结构域上的ELDKWA表位（氨基酸669 - 674）可诱导保护活性。接种疫苗后，RILAVERYLKD二聚体表位疫苗[C(RILAVERYLKDG)2 - BSA]以约1:25,600的稀释度诱导出强烈的表位特异性抗体反应，而ELDKWA四聚体表位疫苗[C-(ELDKWAG)4 - BSA]在小鼠中仍能以1:12,800 - 25,600的抗血清稀释度诱导出对ELDKWA表位的强烈抗体反应，而rgp41亚单位疫苗对这两个表位诱导的抗体反应非常弱（1:400）。在兔实验中，ELDKWA表位疫苗[C-(ELDKWAG)4 - BSA]诱导的ELDKWA表位特异性抗体滴度达到1:6,400，而rgp41亚单位疫苗对该表位以及P1和P2肽诱导的抗体反应非常弱（1:400）。此外，表位疫苗诱导的小鼠和兔抗血清中的ELDKWA表位特异性抗体能与对应于gp41 C结构域的P2肽序列强烈相互作用（稀释度为1:25,600），表位疫苗诱导的小鼠抗血清中的RILAVERYLKD表位特异性抗体也能与对应于gp41 N结构域的P1肽序列强烈相互作用（稀释度为1:102,400）。所有这些结果提供了实验证据，表明表位疫苗可能是诱导高水平抗HIV-1或其他病毒中和抗体的一种新的通用策略。
