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

Seydoux, Emilie; Wan, Yu-Hsin; Feng, Junli; Wall, Abigail; Aljedani, Safia; Homad, Leah J.; MacCamy, Anna J.; Weidle, Connor; Gray, Matthew D.; Brumage, Lauren; Taylor, Justin J.; Pancera, Marie; Stamatatos, Leonidas; McGuire, Andrew T.

doi:10.1016/j.celrep.2021.109084

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

Journal Article · Tue May 04 00:00:00 EDT 2021 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2021.109084· OSTI ID:1816187

Seydoux, Emilie ^[1]; Wan, Yu-Hsin ^[2]; Feng, Junli ^[2]; Wall, Abigail ^[2]; Aljedani, Safia ^[2]; ^[2]; MacCamy, Anna J. ^[2]; Weidle, Connor ^[2]; ^[2]; Brumage, Lauren ^[2]; Taylor, Justin J. ^[3]; Pancera, Marie ^[2]; Stamatatos, Leonidas ^[4]; ^[2]

Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Vaccines and Infectious Diseases Division; OSTI
Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Vaccines and Infectious Diseases Division
Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Vaccines and Infectious Diseases Division; Univ. of Washington, Seattle, WA (United States). Dept. of Global Health; Univ. of Washington, Seattle, WA (United States). Dept. of Immunology
Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Vaccines and Infectious Diseases Division; Univ. of Washington, Seattle, WA (United States). Dept. of Global Health

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 aimAbs; 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.

View Accepted Manuscript (DOE)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231; AC02-76SF00515

OSTI ID:: 1816187

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 5 Vol. 35; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
B cell receptor
HIV-1vaccines
anti-idiotypic antibodies
antibody heavy chain
antibody light chain
broadly neutralizing antibodies

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

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