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

Journal Article · · Nature Medicine
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  1. Fred Hutchinson Cancer Center, Seattle, WA (United States); University of Washington, Seattle, WA (United States)
  2. Fred Hutchinson Cancer Center, Seattle, WA (United States)
  3. Fred Hutchinson Cancer Center, Seattle, WA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  5. Massachusetts Institute of Technology and Harvard, Cambridge, MA (United States)
  6. National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg (South Africa); University of the Witwatersrand, Johannesburg (South Africa)
  7. Duke University, Durham, NC (United States); National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg (South Africa); University of the Witwatersrand, Johannesburg (South Africa)
  8. Duke Univ., Durham, NC (United States). Medical Center
  9. Duke Univ., Durham, NC (United States)
  10. Family Health International, Durham, NC (United States)
  11. Columbia Univ., New York, NY (United States)
  12. University of KwaZulu-Natal, Durban (South Africa)
  13. Universidad Nacional Mayor de San Marcos, Lima (Peru)
  14. University of North Carolina, Chapel Hill, NC (United States)
  15. Beth Israel Deaconess Medical Center, Boston, MA (United States)
  16. University of Cape Town (South Africa)
  17. University of Washington, Seattle, WA (United States)
  18. National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg (South Africa); University of the Witwatersrand, Johannesburg (South Africa); University of KwaZulu-Natal, Durban (South Africa)
+ Show Author Affiliations
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.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
Bill & Melinda Gates Foundation; National Institutes of Health (NIH); USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
89233218CNA000001
OSTI ID:
1887144
Report Number(s):
LA-UR-21-29020
Journal Information:
Nature Medicine, Journal Name: Nature Medicine Journal Issue: 9 Vol. 28; ISSN 1078-8956
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV infections
antibodies
predictive markers