for Allergy and Immunology, CA (United States) The Scripps Research Inst., La Jolla, CA (United States) Univ. The Scripps Research Inst., La Jolla, CA (United States) Ragon Inst., Cambridge, MA (United States).Emory Univ., Atlanta, GA (United States).for Allergy and Immunology, CA (United States) The Scripps Research Inst., La Jolla, CA (United States) The Wistar Inst., Philadelphia, PA (United States).The Scripps Research Inst., La Jolla, CA (United States).for Allergy and Immunology, CA (United States) The Scripps Research Inst., La Jolla, CA (United States) The frequencies of these distinct eOD-GT8 B cell specificities give insights into antigen-specific compositional features of the human naive B cell repertoire and provide actionable information for vaccine design and advancement. These different subclasses within the human repertoire had strong initial affinities (KD) to the immunogen, up to 13 nM, and represent encouraging indications that multiple independent pathways may exist for vaccine-elicited VRC01-class bnAb development in most individuals. Unexpectedly, we also identified naive B cells related to more » the IOMA-class CD4bs bnAb. Non–VRC01-class B cells were also characterized, revealing recurrent public light chain sequences. Multiple naive B cell clones exactly matched mature VRC01-class bnAb L-CDR3 sequences. Several distinct subclasses of VRC01-class naive B cells were identified, sharing sequence characteristics with inferred precursors of known bnAbs VRC01, VRC23, PCIN63, and N6. In this work, we characterized naive human B cells recognizing eOD-GT8, a germline-targeting HIV-1 vaccine candidate immunogen designed to prime VRC01-class Abs. VRC01 is an HIV broadly neutralizing Ab (bnAb) against the envelope CD4-binding site (CD4bs). Assessment of antigen-specific human naive B cells among hundreds of millions of B cells from multiple donors may be used as pre–phase 1 ex vivo human testing to potentially forecast B cell and Ab responses to new vaccine designs. However, the human naive B cell repertoire remains largely undefined. Success of germline-targeting vaccines in humans will depend on the composition of the human naive B cell repertoire, including the frequencies and affinities of epitope-specific B cells. Germline-targeting immunogens have potential to prime protective antibodies (Abs) via more targeted immune responses. Traditional vaccine development to prevent some of the worst current pandemic diseases has been unsuccessful so far.

Binding repertoire biology meaning