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

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

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

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.

Original language	English (US)
Pages (from-to)	336-346.e3
Journal	Cell Host and Microbe
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2019.08.014
State	Published - Sep 11 2019

Keywords

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

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2019.08.014

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Pegu, A., Borate, B., Huang, Y., Pauthner, M. G., Hessell, A. J., Julg, B., Doria-Rose, N. A., Schmidt, S. D., Carpp, L. N., Cully, M. D., Chen, X., Shaw, G. M., Barouch, D. H., Haigwood, N. L., Corey, L., Burton, D. R., Roederer, M., Gilbert, P. B., Mascola, J. R., & Huang, Y. (2019). A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. Cell Host and Microbe, 26(3), 336-346.e3. https://doi.org/10.1016/j.chom.2019.08.014

Pegu, A, Borate, B, Huang, Y, Pauthner, MG, Hessell, AJ, Julg, B, Doria-Rose, NA, Schmidt, SD, Carpp, LN, Cully, MD, Chen, X, Shaw, GM, Barouch, DH, Haigwood, NL, Corey, L, Burton, DR, Roederer, M, Gilbert, PB, Mascola, JR & Huang, Y 2019, 'A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge', Cell Host and Microbe, vol. 26, no. 3, pp. 336-346.e3. https://doi.org/10.1016/j.chom.2019.08.014

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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.",

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AU - Pauthner, Matthias G.

AU - Hessell, Ann J.

AU - Julg, Boris

AU - Doria-Rose, Nicole A.

AU - Schmidt, Stephen D.

AU - Carpp, Lindsay N.

AU - Cully, Michelle D.

AU - Chen, Xuejun

AU - Shaw, George M.

AU - Barouch, Dan H.

AU - Haigwood, Nancy L.

AU - Corey, Lawrence

AU - Burton, Dennis R.

AU - Roederer, Mario

AU - Gilbert, Peter B.

AU - Mascola, John R.

AU - Huang, Ying

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

Abstract

Keywords

ASJC Scopus subject areas

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