Improved Elicitation of Neutralizing Antibodies against Primary Human Immunodeficiency Viruses by Soluble Stabilized Envelope Glycoprotein Trimers

Human immunodeficiency virus (HIV-1) envelope glycoprotein subunits, such as the gp120 exterior glycoprotein, typically elicit antibodies that neutralize T-cell-line-adapted (TCLA), but not primary, clinical isolates of HIV-1. Here we compare the immunogenicity of gp120 and soluble stabilized trimers, which were designed to resemble the functional envelope glycoprotein oligomers of primary and TCLA HIV-1 strains. For both primary and TCLA virus proteins, soluble stabilized trimers generated neutralizing antibody responses more efficiently than gp120 did. Trimers derived from a primary isolate elicited antibodies that neutralized primary and TCLA HIV-1 strains. By contrast, trimers derived from a TCLA isolate generated antibodies that neutralized only the homologous TCLA virus. Thus, soluble stabilized envelope glycoprotein trimers derived from primary HIV-1 isolates represent defined immunogens capable of eliciting neutralizing antibodies that are active against clinically relevant HIV-1 strains.

人类免疫缺陷病毒1型（HIV-1）的包膜糖蛋白亚基（如gp120外膜糖蛋白）通常可诱导产生能够中和T细胞系适应性（T-cell-line-adapted, TCLA）毒株的抗体，但无法中和原发性HIV-1临床分离株。本研究对比了gp120与可溶性稳定三聚体的免疫原性，后者被设计为模拟原发性及TCLA型HIV-1毒株的功能性包膜糖蛋白寡聚体。针对原发性与TCLA型病毒蛋白而言，可溶性稳定三聚体诱导中和抗体应答的效率均优于gp120。源自原发性分离株的三聚体可诱导产生能够中和原发性及TCLA型HIV-1毒株的抗体。与之相反，源自TCLA型分离株的三聚体所诱导产生的抗体仅能中和同源的TCLA型病毒。综上，源自原发性HIV-1分离株的可溶性稳定包膜糖蛋白三聚体，是一类明确的免疫原，能够诱导产生可靶向临床相关HIV-1毒株的中和抗体。