Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

ABSTRACT: Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean IC₈₀s of 0.314 and 0.033 µg mL^-1, respectively. Cryo-EM structures of these nanobodies in complex

SUBMITTER: Xu J 

PROVIDER: S-EPMC11234422 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature