@article{7ff44e5f3801497d867134bb4f1a5077,
title = "A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge",
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",
author = "Amarendra Pegu and Bhavesh Borate and Yunda Huang and Pauthner, {Matthias G.} and Hessell, {Ann J.} and Boris Julg and Doria-Rose, {Nicole A.} and Schmidt, {Stephen D.} and Carpp, {Lindsay N.} and Cully, {Michelle D.} and Xuejun Chen and Shaw, {George M.} and Barouch, {Dan H.} and Haigwood, {Nancy L.} and Lawrence Corey and Burton, {Dennis R.} and Mario Roederer and Gilbert, {Peter B.} and Mascola, {John R.} and Ying Huang",
note = "Funding Information: Support for this work was provided in part by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. This work was also supported in part by NIAID through awards UM1AI068635 (HIV Vaccine Trials Network Statistical and Data Management Center) and R37AI054165 to P.B.G. and awards UM1AI144462 and UM1 AI100663 to D.R.B. Conceptualization: J.R.M. P.B.G. D.R.B. L.C. M.R. and Yunda H.; Methodology: A.P. B.B. P.B.G. J.R.M. and Ying H.; Software: Ying H. and B.B.; Validation: Ying H. and B.B.; Formal Analysis: Ying H. and B.B.; Investigation: A.P. M.G.P. M.D.C. and X.C.; Resources: A.J.H. B.J. N.A.D.-R. S.D.S. D.H.B. N.L.H. and G.M.S; Data Curation: A.P. M.G.P. and L.N.C.; Writing ? original draft: A.P. Ying H. and B.B.; Writing: A.P. Ying H. and B.B.; Review and Editing: Yunda H. M.G.P. A.J.H. B.J. N.D.R. S.D.S. L.N.C. D.H.B. N.L.H. L.C. D.R.B. M.R. P.B.G. and J.R.M.; Visualization: Ying H. B.B. and L.N.C.; Supervision: D.R.B. M.R. P.B.G. and J.R.M.; Funding acquisition: P.B.G. L.C. and J.R.M. 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 the HIV Vaccine Trials Network and the Scientific Advisory Working Group of the Vaccine Research Center and is a paid consultant of IAVI. Funding Information: Support for this work was provided in part by the Intramural Research Program of the Vaccine Research Center , National Institute of Allergy and Infectious Diseases (NIAID), NIH. This work was also supported in part by NIAID through awards UM1AI068635 ( HIV Vaccine Trials Network Statistical and Data Management Center ) and R37AI054165 to P.B.G. and awards UM1AI144462 and UM1 AI100663 to D.R.B. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = sep,
day = "11",
doi = "10.1016/j.chom.2019.08.014",
language = "English (US)",
volume = "26",
pages = "336--346.e3",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",
}