Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization.

ABSTRACT: Broadly HIV-1 neutralizing VRC01 class antibodies target the CD4-binding site of Env. They are derived from VH1-2^∗02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on naive B cells have been designed and evaluated in knockin mice. However, the elicited antibodies cannot bypass glycans present on the conserved position N276 of Env, which restricts access to the CD4-binding site. Efforts to guide the appropriate maturation of these antibodies by sequential immunization have not yet been successful. Here, we report on a two-step immunization scheme that leads to

SUBMITTER: Parks KR 

PROVIDER: S-EPMC6936959 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature