A single, continuous metric to define tiered serum neutralization potency against HIV

  1. Peter Hraber  Is a corresponding author
  2. Bette Korber
  3. Kshitij Wagh
  4. David Montefiori
  5. Mario Roederer
  1. Los Alamos National Laboratory, United States
  2. Duke University Medical Center, United States
  3. National Institute for Allergy and Infectious Diseases, United States

Abstract

HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization-sensitivity phenotype. This helped to recognize that tier-1 neutralization responses can be elicited readily, but do not protect against new infections. Tier-3 viruses are the least sensitive to neutralization. Because most circulating viruses are tier 2, vaccines that elicit neutralization responses against them are needed. While tier classification is widely used for viruses, a way to rate serum or antibody neutralization responses in comparable terms is needed. Logistic regression of neutralization outcomes summarizes serum or antibody potency on a continuous, tier-like scale. It also tests significance of the neutralization score, to indicate cases where serum response does not depend on virus tiers. The method can standardize results from different virus panels, and could lead to high-throughput assays, which evaluate a single serum dilution, rather than a dilution series, for more efficient use of limited resources to screen samples from vaccinees.

Article and author information

Author details

  1. Peter Hraber

    Theroetical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, United States
    For correspondence
    phraber@lanl.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2920-4897
  2. Bette Korber

    Theroetical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kshitij Wagh

    Theroetical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David Montefiori

    Department of Surgery, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mario Roederer

    Vaccine Research Center, National Institute for Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

Bill and Melinda Gates Foundation (OPP1146996)

  • Peter Hraber
  • Bette Korber
  • Kshitij Wagh
  • David Montefiori

National Institute of Allergy and Infectious Diseases

  • Mario Roederer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Peter Hraber
  2. Bette Korber
  3. Kshitij Wagh
  4. David Montefiori
  5. Mario Roederer
(2018)
A single, continuous metric to define tiered serum neutralization potency against HIV
eLife 7:e31805.
https://doi.org/10.7554/eLife.31805

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https://doi.org/10.7554/eLife.31805