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Cell Host Microbe. 2019 Sep 11;26(3):336-346.e3. doi: 10.1016/j.chom.2019.08.014.

A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
4
Department of Immunology & Microbiology, IAVI Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunogen Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR 97006, USA.
6
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
7
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
8
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
9
Department of Immunology & Microbiology, IAVI Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunogen Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
10
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
11
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@mail.nih.gov.
12
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA. Electronic address: yhuang@fredhutch.org.

Abstract

Passively administered broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have been shown to protect non-human primates (NHPs) against chimeric simian-human immunodeficiency virus (SHIV) infection. With data from multiple non-human primate SHIV challenge studies that used single bNAbs, we conducted a meta-analysis to examine the relationship between predicted serum 50% neutralization titer (ID50) against the challenge virus and infection outcome. In a logistic model that adjusts for bNAb epitopes and challenge viruses, serum ID50 had a highly significant effect on infection risk (p < 0.001). The estimated ID50 to achieve 50%, 75%, and 95% protection was 91 (95% confidence interval [CI]: 55, 153), 219 (117, 410), and 685 (319, 1471), respectively. This analysis indicates that serum neutralizing titer against the relevant virus is a key parameter of protection and that protection from acquisition by a single bNAb might require substantial levels of neutralization at the time of exposure.

KEYWORDS:

SHIV challenge; broad neutralizing antibodies; correlates of protection; meta-analysis; non-human primate studies

PMID:
31513771
PMCID:
PMC6755677
[Available on 2020-09-11]
DOI:
10.1016/j.chom.2019.08.014

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