A tremendous loss of financial and human resources from seven large-scale HIV vaccine efficacy trials suggest a need for a systematic approach to vaccine selection. We conducted a systematic analysis of three important envelope glycoprotein (Env) vaccine candidates: BG505 SOSIP.664, 1086.C gp140, and 1086.C gp120 to determine the most promising by comparing their structure and antigenicity. We found that the BG505 SOSIP trimer and 1086.C gp140 clearly outperformed the 1086.C gp120 monomer. BG505 SOSIP.664 bound the strongest to the most potent and broadest broadly neutralizing antibodies (bnAbs) PG9, PGT145, VRC01, and PGT121. Of interest, although BG505 SOSIP.664 did not bind to the CH58 mAb, 1086.C gp140 bound strongly to this mAb, which belongs to a class of non-neutralizing antibodies that may be protective based on correlates of protection studies of the RV144 HIV vaccine trial. The 1086.C gp120 monomer was the least antigenic of the three vaccine immunogens, binding the weakest to bnAbs and CH58 mAb. Taken together, the evidence provided here combined with previous preclinical immunogenicity and efficacy data strongly argue that the BG505 SOSIP.664 trimer and 1086.C gp140 are likely to be better vaccine immunogens than the monomeric 1086.C gp120, which was just recently tested and shown to be nonefficacious in a phase IIb/III trial. Thus, to best utilize our financial and valuable human resources, we propose a systematic approach by not only comparing structure and antigenicity, but also immunogenicity and efficacy of Env vaccine candidates in the preclinical phase to the selection of only the most promising vaccine candidates for clinical testing.

中文翻译：

---

HIV-1 疫苗免疫原选择的系统方法。

七项大规模 HIV 疫苗效力试验造成的财政和人力资源的巨大损失表明需要一种系统的疫苗选择方法。我们对三种重要的包膜糖蛋白 (Env) 候选疫苗进行了系统分析：BG505 SOSIP.664、1086.C gp140 和 1086.C gp120，通过比较它们的结构和抗原性来确定最有希望的疫苗。我们发现 BG505 SOSIP 三聚体和 1086.C gp140 明显优于 1086.C gp120 单体。BG505 SOSIP.664 与最有效和最广泛的广泛中和抗体 (bnAbs) PG9、PGT145、VRC01 和 PGT121 结合最强。有趣的是，尽管 BG505 SOSIP.664 不与 CH58 mAb 结合，但 1086.C gp140 与该 mAb 结合强烈，它属于一类非中和抗体，根据 RV144 HIV 疫苗试验的保护研究相关性可能具有保护作用。1086.C gp120 单体是三种疫苗免疫原中抗原性最低的，与 bnAb 和 CH58 mAb 的结合最弱。综上所述，此处提供的证据与之前的临床前免疫原性和功效数据相结合，强烈认为 BG505 SOSIP.664 三聚体和 1086.C gp140 可能是比单体 1086.C gp120 更好的疫苗免疫原，后者刚刚经过测试并在 IIb/III 期试验中显示无效。因此，为了最好地利用我们的财务和宝贵的人力资源，我们提出了一种系统方法，不仅通过比较结构和抗原性，