| Literature DB >> 34986348 |
Amarendra Pegu1, Ling Xu2, Megan E DeMouth1, Giulia Fabozzi1, Kylie March1, Cassandra G Almasri1, Michelle D Cully1, Keyun Wang1, Eun Sung Yang1, Joana Dias1, Christine M Fennessey3, Jason Hataye1, Ronnie R Wei2, Ercole Rao2, Joseph P Casazza1, Wanwisa Promsote1, Mangaiarkarasi Asokan1, Krisha McKee1, Stephen D Schmidt1, Xuejun Chen1, Cuiping Liu1, Wei Shi1, Hui Geng1, Kathryn E Foulds1, Shing-Fen Kao1, Amy Noe1, Hui Li4, George M Shaw4, Tongqing Zhou1, Constantinos Petrovas1, John-Paul Todd1, Brandon F Keele3, Jeffrey D Lifson3, Nicole A Doria-Rose1, Richard A Koup1, Zhi-Yong Yang2, Gary J Nabel5, John R Mascola6.
Abstract
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here, a trispecific bNAb reduces viremia 100- to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounds transiently and returns to low levels, through CD8-mediated immune control. These viruses remain sensitive to the trispecific antibody, despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppresses the emergence of resistance in viruses derived from HIV-1-infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 neutralizing antibodies, therefore, mediate potent antiviral activity in vivo and may minimize the potential for immune escape.Entities:
Mesh：
Substances：
Year: 2022 PMID： 34986348 PMCID： PMC8767641 DOI： 10.1016/j.celrep.2021.110199
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423