HIV-1包膜糖蛋白免疫策略对抗体产生的影响
首发时间:2017-05-12
摘要:目的研究来源于一个I型人类免疫缺陷病毒(human immunodeficiency virus type 1, HIV-1)慢性感染的广谱中和者包膜糖蛋白(Env)的免疫原性及免疫策略对抗体生成的影响。方法 gp120单体(gp120M)、gp140单体(gp140M)、gp120三聚体(gp120T)和gp140三聚体(gp140T)蛋白不同免疫策略免疫BALB/c小鼠。末次免疫后14天测定血清中特异性结合抗体、中和抗体滴度。结果包膜gp120和gp140免疫小鼠后,血清抗体对异源(HIV-1毒株SF162、JRCSF、Bal和IIIB)及同源HIV-1包膜抗原(06044 gp120M、gp120T和gp140T)显示出广谱结合能力;部分动物血清显示了中和SF162假病毒的能力;DNA初免-蛋白加强策略诱导结合抗体和中和抗体能力均明显优于单纯蛋白免疫(P<0.05)。结论 HIV-1广谱中和者包膜糖蛋白单体和三聚体均显示了良好的免疫原性;DNA初免-蛋白加强策略诱导结合抗体和中和抗体能力显著好于单纯蛋白免疫。
关键词: HIV-1 包膜糖蛋白 广谱中和抗体 三聚体 免疫原性
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Influence of immunization regimens of HIV-1 envelope on antibody production
Abstract:In this paper, we aimed to explore the immunogenicity of HIV-1 envelope derived from a broad neutralizer and the influence of different immunization regimens on humoral immune response. Balb/c mice were immunized with DNA or protein immunogens of monomeric gp120 (gp120M), monomeric gp140 (gp140M), trimeric gp120 (gp120T), or, trimeric gp140 (gp140T) in a variety of immunization regimens. Then the binding antibody titers and neutralizing antibody titers of the sera from immunized mice at day14 after final immunization were determined. We found that the immunization with gp120 or gp140 derived from the broad neutralizer induced high titers of specific binding antibodies, showing broadly binding ability to heterologous Env antigens. The immunization with the Envs under different regimens induced different binding antibody titers. The regimen "DNA prime-protein boost" was superior to the regimen" protein alone" (P<0.05). Env-immunized sera from part mice showed neutralizing activity against heterologous SF162 virus and homologous 06044 virus. Different immunization regimen resulted in significantly different serum neutralizing antibody titers. In conclusion, gp120 and gp140 derived from the HIV-1 broad neutralizer can induce broadly binding antibodies. Compared immmunization using the regimen "protein alone", immunization using the regimen "DNA prime-protein boost" induces more robust binding and neutralizing antibody responses.
Keywords: HIV-1 envelop glycoprotein broadly neutralizing antibody immunogenicity
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