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Science. 2017 Oct 6;358(6359):85-90. doi: 10.1126/science.aan8630. Epub 2017 Sep 20.

Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques.

Author information

1
Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
2
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
3
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
4
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
5
Department of Immunology and Microbiology, International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
6
National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
7
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. gary.nabel@sanofi.com jmascola@mail.nih.gov.
8
Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA. gary.nabel@sanofi.com jmascola@mail.nih.gov.

Abstract

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.

PMID:
28931639
PMCID:
PMC5978417
DOI:
10.1126/science.aan8630
[Indexed for MEDLINE]
Free PMC Article

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