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

Amarendra Pegu¹, Bhavesh Borate², Yunda Huang³, Matthias G Pauthner⁴, Ann J Hessell⁵, Boris Julg⁶, Nicole A Doria-Rose¹, Stephen D Schmidt¹, Lindsay N Carpp², Michelle D Cully¹, Xuejun Chen¹, George M Shaw⁷, Dan H Barouch⁸, Nancy L Haigwood⁵, Lawrence Corey², Dennis R Burton⁹, Mario Roederer¹, Peter B Gilbert¹⁰, John R Mascola¹¹, Ying Huang¹²

Affiliations

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.

PMID: 31513771
PMCID: PMC6755677
DOI: 10.1016/j.chom.2019.08.014

Meta-Analysis

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

Amarendra Pegu et al. Cell Host Microbe. 2019.

. 2019 Sep 11;26(3):336-346.e3.

doi: 10.1016/j.chom.2019.08.014.

Authors

Affiliations

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.

PMID: 31513771
PMCID: PMC6755677
DOI: 10.1016/j.chom.2019.08.014

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.

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Conflict of interest statement

Declaration of Interests: John Mascola and Mario Roederer are listed as inventors on NIH patents, or patent applications for 10E8, N6LS, VRC01, VRC01LS, and VRC07–523LS. Dennis Burton is listed as an inventor on patents for b12, PG9, PGT121, PGT126, and PGDM1400. He is also on the Executive Advisory Board of HVTN and the SAWG of the VRC and is a paid consultant of IAVI.

Figures

**Figure 1.. Passive immunization studies in NHPs.**
Information on the passive immunization NHP studies used for the meta-analysis, organized by research group.

**Figure 2.. Association of protection with serum ID50 titer for different SHIVs.**
The curves for each indicated SHIV strain depict the estimated level of protection as a function of serum ID50 titer for bNabs targeting various epitopes in the study dataset. The 95% bootstrap confidence intervals for ID50 titers required to achieve 50%, 75%, and 95% protection are represented by the three colored horizontal lines on each curve. See also Figures S1 and S2.

**Figure 3.. Association of protection with serum ID50 titers averaging over all epitope and virus combinations.**
The 95% bootstrap confidence intervals for ID50 titers required to achieve 50%, 75%, and 95% protection are represented by the three horizontal lines on the curve. See also Figure S3.

See this image and copyright information in PMC

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

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

Authors

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Abstract

Conflict of interest statement

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