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 five 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 naïve B cells have been designed and evaluated in knock-in 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 led to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. Our results are relevant to clinical trials aiming to elicit VRC01 antibodies.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens Human Immunodeficiency Virus 1

SUBMITTER: Andrew Borst  

LAB HEAD: David Veesler

PROVIDER: PXD015168 | Pride | 2020-05-26

REPOSITORIES: Pride