A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies

A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies

Summary: Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cr...

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Main Authors: Evan M. Cale, Chen-Hsiang Shen, Adam S. Olia, Nathan A. Radakovich, Reda Rawi, Yongping Yang, David R. Ambrozak, Anthony K. Bennici, Gwo-Yu Chuang, Emma D. Crooks, Jefferson I. Driscoll, Bob C. Lin, Mark K. Louder, Patrick J. Madden, Michael A. Messina, Keiko Osawa, Guillaume B.E. Stewart-Jones, Raffaello Verardi, Zoe Vrakas, Danielle Xie, Baoshan Zhang, James M. Binley, Mark Connors, Richard A. Koup, Theodore C. Pierson, Nicole A. Doria-Rose, Peter D. Kwong, John R. Mascola, Jason Gorman
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Cell Reports
Subjects:
CP: Immunology
CP: Molecular biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724013615
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Summary:Summary: Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.01 in complex with the Env trimer reveals binding to the same gp120-gp41 interface site of vulnerability as antibody 35O22 from a different HIV-1-infected donor. In addition to having similar angles of approach and extensive contacts with glycans N88 and N625, VRC44 and 35O22 derive from the same IGHV1-18 gene and share convergent mutations, indicating these two antibodies to be members of the only known highly glycan-dependent multidonor class. Strikingly, both lineages achieved almost 100% neutralization breadth against virus strains displaying high-mannose glycans. The high breadth and reproducible elicitation of VRC44 and 35O22 lineages validate germline-based methods of immunogen design for targeting the HIV-1 gp120-gp41 interface.
ISSN:2211-1247

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