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 | |
| State | Published - Sep 11 2019 |
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Keywords
- broad neutralizing antibodies
- correlates of protection
- meta-analysis
- non-human primate studies
- SHIV challenge
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology
Cite this
A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge. / Pegu, Amarendra; Borate, Bhavesh; Huang, Yunda; Pauthner, Matthias G.; Hessell, Ann; Julg, Boris; Doria-Rose, Nicole A.; Schmidt, Stephen D.; Carpp, Lindsay N.; Cully, Michelle D.; Chen, Xuejun; Shaw, George M.; Barouch, Dan H.; Haigwood, Nancy; Corey, Lawrence; Burton, Dennis R.; Roederer, Mario; Gilbert, Peter B.; Mascola, John R.; Huang, Ying.
In: Cell Host and Microbe, Vol. 26, No. 3, 11.09.2019, p. 336-346.e3.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge
AU - Pegu, Amarendra
AU - Borate, Bhavesh
AU - Huang, Yunda
AU - Pauthner, Matthias G.
AU - Hessell, Ann
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
AU - Corey, Lawrence
AU - Burton, Dennis R.
AU - Roederer, Mario
AU - Gilbert, Peter B.
AU - Mascola, John R.
AU - Huang, Ying
PY - 2019/9/11
Y1 - 2019/9/11
N2 - 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.
AB - 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.
KW - broad neutralizing antibodies
KW - correlates of protection
KW - meta-analysis
KW - non-human primate studies
KW - SHIV challenge
UR - http://www.scopus.com/inward/record.url?scp=85071461255&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071461255&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2019.08.014
DO - 10.1016/j.chom.2019.08.014
M3 - Article
C2 - 31513771
AN - SCOPUS:85071461255
VL - 26
SP - 336-346.e3
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 3
ER -