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

Amarendra Pegu; Bhavesh Borate; Yunda Huang; Matthias G Pauthner; Ann J Hessell; Boris Julg; Nicole A Doria-Rose; Stephen D Schmidt; Lindsay N Carpp; Michelle D Cully; Xuejun Chen; George M Shaw; Dan H Barouch; Nancy L Haigwood; Lawrence Corey; Dennis R Burton; Mario Roederer; Peter B Gilbert; John R Mascola; Ying Huang

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

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

Authors

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.

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.

Publication types

Meta-Analysis

MeSH terms

Animals
Antibodies, Neutralizing / administration & dosage*
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology*
Antibodies, Viral / blood
Antibodies, Viral / immunology
Epitopes / immunology
Female
HIV Infections / immunology
Immunization, Passive*
Inhibitory Concentration 50
Logistic Models
Macaca mulatta
Male
Simian Acquired Immunodeficiency Syndrome / immunology*
Simian Acquired Immunodeficiency Syndrome / prevention & control*
Simian Acquired Immunodeficiency Syndrome / virology
Simian Immunodeficiency Virus / immunology*
env Gene Products, Human Immunodeficiency Virus / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Epitopes
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding