Structural highlights
Publication Abstract from PubMedAn 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. Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies.,Seydoux E, Wan YH, Feng J, Wall A, Aljedani S, Homad LJ, MacCamy AJ, Weidle C, Gray MD, Brumage L, Taylor JJ, Pancera M, Stamatatos L, McGuire AT Cell Rep. 2021 May 4;35(5):109084. doi: 10.1016/j.celrep.2021.109084. PMID:33951425[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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