HVTN703/HPTN081 + HVTN704/HPTN085 Neutralization Titer Biomarker (PT80)

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT80 of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. Based on this result, we suggest that the goal of sustained PT80 <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT80 biomarker as a surrogate endpoint for evaluation of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.抗体介导预防（Antibody Mediated Prevention, AMP）试验结果表明，广谱中和抗体（broadly neutralizing antibody, bnAb）VRC01可预防人类免疫缺陷病毒1型（HIV-1）VRC01敏感株的感染。本研究利用AMP试验数据证实，预测血清中和80%抑制稀释度效价（PT80）这一生物标志物——该标志物可量化个体血清中抗体针对某一HIV-1分离株的中和效力——可用于预测HIV-1的预防效果。与非人灵长类动物研究结果一致，本研究估算得到：若要针对目标暴露病毒群体实现90%的感染预防效果，需达到平均200的PT80值（即体外实验中，将感染风险降低80%所需抗体浓度的200倍）。基于该结果，我们提出，通过工程化改造获得长半衰期的广谱中和抗体给药方案，有望实现针对90%循环毒株的持续PT80＜200的目标。本研究建议将PT80生物标志物作为广谱中和抗体给药方案评估的替代终点，同时可作为诱导广谱中和抗体的候选疫苗的性能基准工具。