Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class
The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques. The nAbs displayed low potency but up to 90% breadth on a 20-strain SIV panel. Crystal structures of representative nAbs in complex with SIV MPER peptides revealed the SIV antibodies to bind a helical epitope at the N-terminal (proximal) region of the MPER, defining a reproducible multi-donor class encompassing all four lineages. HIV-1 comparison showed that this class of SIV MPER-directed antibodies targets a helical region overlapping that targeted by human vaccine-elicited ones. Thus, a prevalent and reproducible class of SIV bnAbs recognizes an epitope similar to that recently observed in an HIV-1-vaccine trial.
Authors
- Rosemarie D. Mason (ORCID: https://orcid.org/0000-0001-7123-4902)
- Richard Nguyen (ORCID: https://orcid.org/0000-0003-2453-3461)
- Jason Gorman (ORCID: https://orcid.org/0000-0002-3775-6560)
- Renguang Du
- Yongping Yang (ORCID: https://orcid.org/0000-0002-8307-1095)
- David R. Ambrozak (ORCID: https://orcid.org/0000-0003-1038-7328)
- Daniel C. Douek (ORCID: https://orcid.org/0000-0001-5575-8634)
- Chaim A. Schramm
- Peter D. Kwong (ORCID: https://orcid.org/0000-0003-3560-232X)
- Christopher A. Gonelli (ORCID: https://orcid.org/0000-0002-7521-8528)
- Aliaksandr Druz
- Hannah A. D. King (ORCID: https://orcid.org/0000-0002-7575-198X)
- Kimberly Manalang
- Chen‐Hsiang Shen (ORCID: https://orcid.org/0000-0002-9560-3992)
- Cheng Cheng (ORCID: https://orcid.org/0000-0002-3837-9293)
- Mario Roederer (ORCID: https://orcid.org/0000-0001-7448-7040)
- Yen‐Ting Lai (ORCID: https://orcid.org/0000-0003-3700-6417)
- Kaimei Song
- Mohammed S. Ahmadi
Institutions
- National Institutes of Health (US)
- Center for Biologics Evaluation and Research (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115163
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Energy
- National Institutes of Health
- Office of Science
- National Institute of Allergy and Infectious Diseases
- Basic Energy Sciences