Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
Nat Med. 2022 Sep;28(9):1924-1932. doi: 10.1038/s41591-022-01953-6. Epub 2022 Aug 22.
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 (PT) 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 PT 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 PT <200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT biomarker as a surrogate endpoint for evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.
抗体介导的预防试验表明，广泛中和抗体（bnAb）VRC01 可预防对 VRC01 敏感的人类免疫缺陷病毒 1（HIV-1）的获得。利用 AMP 试验数据，我们在此表明，预测血清中和 80%抑制稀释倍数滴度（PT）的生物标志物-量化个体血清中抗体对 HIV-1 分离株的中和效力-可用于预测 HIV-1 的预防效果。与非人类灵长类动物研究的结果相似，估计需要针对可能暴露的病毒群体的平均 PT 为 200（意味着 bnAb 浓度比在体外减少 80%感染所需的浓度高 200 倍），才能实现对这些病毒获得性感染的 90%预防效果。基于这一结果，我们建议通过设计具有长半衰期的有前途的 bnAb 方案，将持续 PT<200 针对 90%循环病毒的目标作为评估 bnAb 方案的替代终点，并作为基准候选 bnAb 诱导疫苗的工具。
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