Journal
SCIENCE
Volume 358, Issue 6359, Pages 85-89Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan8630
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Funding
- Sanofi Global RD
- National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research and Vaccine Research Center
- NIH [AI096040, AI124377, AI126603]
- NIAID [UM1AI100663]
- IAVI
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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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