The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consistently but at a wide range of titers and with incompletely determined specificities. A precise delineation of immunogenic neutralization epitopes on native-like trimers could help strategies to extend the NAb response to heterologous HIV-1 strains. One autologous NAb epitope on the BG505 Env trimer is known to involve residues lining a hole in the glycan shield that is blocked by adding a glycan at either residue 241 or 289. This glycan-hole epitope accounts for the NAb response of most trimer-immunized rabbits but not for that of a substantial subset. Here, we have used a large panel of mutant BG505 Env-pseudotyped viruses to define additional sites. A frequently immunogenic epitope in rabbits is blocked by adding a glycan at residue 465 near the junction of the gp120 V5 loop and β24 strand and is influenced by amino-acid changes in the structurally nearby C3 region. We name this new site the “C3/465 epitope”. Of note is that the C3 region was under selection pressure in the infected infant from whom the BG505 virus was isolated. A third NAb epitope is located in the V1 region of gp120, although it is rarely immunogenic. In macaques, NAb responses induced by BG505 SOSIP trimers are more often directed at the C3/465 epitope than the 241/289-glycan hole.

基于BG505进化枝A env的类似天然的可溶性SOSIP.664三聚体HIV-1基因在多种动物中具有免疫原性，其中研究最多的是兔子和恒河猴。三聚体一致地诱导自体中和抗体（NAbs），但是滴度范围很广，特异性还不完全确定。在天然样三聚体上精确描述免疫原性中和表位可以帮助策略将NAb反应扩展至异源HIV-1菌株。已知BG505 Env三聚体上的一个自体NAb表位涉及在糖基盾构孔上排成一行的残基，该残基通过在残基241或289处添加糖基来封闭。该糖基孔表位解释了大多数三聚体免疫的NAb反应兔子，但不是相当一部分。在这里，我们使用了大量的突变BG505 Env假型病毒来定义其他位点。通过在gp120 V5环与β24链交界处附近的465位残基处添加一个聚糖，可阻断兔中常见的免疫原性表位，并受到结构附近C3区氨基酸变化的影响。我们将此新站点命名为“ C3 / 465表位”。值得注意的是，在从中分离出BG505病毒的受感染婴儿中，C3区处于选择压力之下。第三个NAb表位位于gp120的V1区域，尽管很少具有免疫原性。在猕猴中，与241 / 289-聚糖孔相比，BG505 SOSIP三聚体诱导的NAb反应更经常针对C3 / 465表位。我们将此新站点命名为“ C3 / 465表位”。值得注意的是，在从中分离出BG505病毒的受感染婴儿中，C3区处于选择压力之下。第三个NAb表位位于gp120的V1区域，尽管很少具有免疫原性。在猕猴中，与241 / 289-聚糖孔相比，BG505 SOSIP三聚体诱导的NAb反应更经常针对C3 / 465表位。我们将此新站点命名为“ C3 / 465表位”。值得注意的是，在从中分离出BG505病毒的受感染婴儿中，C3区处于选择压力之下。第三个NAb表位位于gp120的V1区域，尽管很少具有免疫原性。在猕猴中，与241 / 289-聚糖孔相比，BG505 SOSIP三聚体诱导的NAb反应更经常针对C3 / 465表位。