A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention.

ABSTRACT: Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structure-based design with a matrix-based approach to generate VRC01-class variants that filled an interfacial cavity, used diverse third-complementarity-determining regions, reduced potential steric clashes, or exploited extended contacts to a neighboring protomer within the envelope trimer. On a 208-strain panel, variant VRC01.23LS neutralized 90% of the panel at a geometric mean IC₈₀ less than 1 μg/ml, and in transgenic mice with human neonatal-Fc receptor, the serum half-life of VRC01.23LS was indistinguishable from that of the parent VRC01LS, wh

SUBMITTER: Kwon YD 

PROVIDER: S-EPMC8331036 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature