Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition

Gilbert P.B.; Huang Y.; deCamp A.C.; Karuna S.; Zhang Y.; Magaret C.A.; Giorgi E.E.; Korber B.; Edlefsen P.T.; Rossenkhan R.; Juraska M.; Rudnicki E.; Kochar N.; Huang Y.; Carpp L.N.; Barouch D.H.; Mkhize N.N.; Hermanus T.; Kgagudi P.; Bekker V.; Kaldine H.; Mapengo R.E.; Eaton A.; Domin E.; West C.; Feng W.; Tang H.; Seaton K.E.; Heptinstall J.; Brackett C.; Chiong K.; Tomaras G.D.; Andrew P.; Mayer B.T.; Reeves D.B.; Sobieszczyk M.E.; Garrett N.; Sanchez J.; Gay C.; Makhema J.; Williamson C.; Mullins J.I.; Hural J.; Cohen M.S.; Corey L.; Montefiori D.C.; Morris L. · Nature Medicine (2022) · DOI: 10.1038/s41591-022-01953-6

Resumen

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 evaluatinon of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.

Instituciones: Universidad Nacional Mayor de San Marcos