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

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.

Authors:

Hraber, Peter Thomas  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-2920-4897"
• Search orcid.org for ORCID "0000-0002-2920-4897"

Korber, Bette Tina Marie  ^[2];

• Search DOE PAGES for author "Korber, Bette Tina Marie"
• Search DOE PAGES for ORCID "0000-0002-2026-5757"
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Wagh, Kshitij ^[1]; Montefiori, David ^[3]; Roederer, Mario ^[4]

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+ Show Author Affiliations

1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos (United States)
3. Duke Univ., Durham, NC (United States). Medical Center, Dept. of Surgery
4. National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center, National Inst. of Allergy and Infectious Diseases

Publication Date:

2018-01-19

Research Org.:

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE; National Institutes of Health (NIH); Bill and Melinda Gates Foundation

Contributing Org.:

Duke University

OSTI Identifier:

1419748

Report Number(s):

LA-UR-16-29342
Journal ID: ISSN 2050-084X

Grant/Contract Number:  

AC52-06NA25396

Resource Type:

Accepted Manuscript

Journal Name:

eLife

Additional Journal Information:

Journal Volume: 7; Journal ID: ISSN 2050-084X

Publisher:

eLife Sciences Publications, Ltd.

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; Biological Science