Title
Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition
Date Issued
01 September 2022
Access level
open access
Resource Type
journal article
Author(s)
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.
Publisher(s)
Nature Research
Abstract
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.
Start page
1924
End page
1932
Volume
28
Issue
9
Language
English
OCDE Knowledge area
Virología
Subjects
Scopus EID
2-s2.0-85136949986
PubMed ID
Source
Nature Medicine
ISSN of the container
10788956
Sources of information:
Directorio de Producción Científica
Scopus