|Title||Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Xu L, Pegu A, Rao E, Doria-Rose N, Beninga J, McKee K, Lord DM, Wei RR, Deng G, Louder M, Schmidt SD, Mankoff Z, Wu L, Asokan M, Beil C, Lange C, Leuschner WDirk, Kruip J, Sendak R, Kwon YDo, Zhou T, Chen X, Bailer RT, Wang K, Choe M, Tartaglia LJ, Barouch DH, O'Dell S, Todd J-P, Burton DR, Roederer M, Connors M, Koup RA, Kwong PD, Yang Z-Y, Mascola JR, Nabel GJ|
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.
|Grant List||U19 AI096040 / AI / NIAID NIH HHS / United States |
UM1 AI124377 / AI / NIAID NIH HHS / United States
UM1 AI126603 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques.