Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques

Xu, Ling; Pegu, Amarendra; Rao, Ercole; Doria-Rose, Nicole; Beninga, Jochen; McKee, Krisha; Lord, Dana M.; Wei, Ronnie R.; Deng, Gejing; Louder, Mark; Schmidt, Stephen D.; Mankoff, Zachary; Wu, Lan; Asokan, Mangaiarkarasi; Beil, Christian; Lange, Christian; Leuschner, Wulf Dirk; Kruip, Jochen; Sendak, Rebecca; Do Kwon, Young; Zhou, Tongqing; Chen, Xuejun; Bailer, Robert T.; Wang, Keyun; Choe, Misook; Tartaglia, Lawrence J.; Barouch, Dan H.; O’Dell, Sijy; Todd, John-Paul; Burton, Dennis R.; Roederer, Mario; Connors, Mark; Koup, Richard A.; Kwong, Peter D.; Yang, Zhi-yong; Mascola, John R.; Nabel, Gary J.

doi:10.1126/science.aan8630

Title: Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques

Journal Article · Fri Oct 06 00:00:00 EDT 2017 · Science

DOI:https://doi.org/10.1126/science.aan8630· OSTI ID:1438883

Xu, Ling ^[1];

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^[1]; McKee, Krisha ^[2];

^[1]; Wei, Ronnie R. ^[1]; Deng, Gejing ^[1];

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^[2]; Mankoff, Zachary ^[2]; Wu, Lan ^[1]; Asokan, Mangaiarkarasi ^[2];

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Sanofi, Cambridge, MA (United States)
National Inst. of Allergy and Infectious Diseases, Bethesda, MD (United States)
Harvard Medical School, Boston, MA (United States); Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA (United States)
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA (United States); The Scripps Research Inst., La Jolla, CA (United States)

The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1438883

Journal Information:: Science, Vol. 358, Issue 6359; ISSN 0036-8075

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 181 works

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Antibody-mediated prevention and treatment of HIV-1 infection Gruell, Henning; Klein, Florian Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0455-9	journal	November 2018
HIV-2 as a model to identify a functional HIV cure Esbjörnsson, Joakim; Jansson, Marianne; Jespersen, Sanne AIDS Research and Therapy, Vol. 16, Issue 1 https://doi.org/10.1186/s12981-019-0239-x	journal	September 2019
Antibodies and Antibody Derivatives: New Partners in HIV Eradication Strategies Carrillo, Jorge; Clotet, Bonaventura; Blanco, Julià Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.02429	journal	October 2018
V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers Duerr, Ralf; Gorny, Miroslaw K. Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030082	journal	August 2019

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