Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies

Cell Reports

Marie Pancera¹  Leonidas Stamatatos²  Justin J. Taylor³  Yu-Hsin Wan³  Lauren Brumage³  Junli Feng³  Abigail Wall³  Anna J. MacCamy³  Connor Weidle³  Leah J. Homad³  Matthew D. Gray³  Andrew T. McGuire³  Emilie Seydoux³  Safia Aljedani³ 

[1] University of Washington, Department of Global Health, Seattle, WA 98195, USA;University of Washington, Department of Immunology, Seattle, WA 98109, USA;Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA;

关键词: HIV-1;    vaccines;    anti-idiotypic antibodies;    broadly neutralizing antibodies;    B cell receptor;    antibody light chain;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo.

【 授权许可】

Unknown