Removal of variable domain <i>N</i>-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.

ABSTRACT: Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically. Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products. Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed. When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however,

SUBMITTER: Chuang GY 

PROVIDER: S-EPMC7643989 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature