ArticlebioRxiv : the preprint server for biology2025
CryoEM Structures of Antibodies Elicited by Germline-Targeting HIV MPER Epitope-Scaffolds.
Jiachen Huang, Olivia M Swanson, Kimmo Rantalainen, Monica L Fernández-Quintero, Johannes R Loeffler, Ryan Tingle, Erik Georgeson, Nicole Phelps, Gabriel Ozorowski, Torben Schiffner and 2 more
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In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
12 authors.
Jiachen HuangDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-7624-7390 Olivia M SwansonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-8162-8358 Kimmo RantalainenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-3158-9183 Monica L Fernández-QuinteroDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Johannes R LoefflerDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Ryan TingleDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Erik GeorgesonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nicole PhelpsDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-9695-8138 Torben SchiffnerDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
William R SchiefDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-7153-3769 Funding
Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6MGlycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8MDevelopment of soluble and membrane bound immunogens to shepherd HIV-1 MPER specific BCR maturationF31AI179426 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Olivia Swanson · 2024 to 2026
$107kGates Foundation INV-007522Gates Foundation INV-008813Gates Foundation INV-034657NIAID NIH HHS F31 AI179426NIAID NIH HHS R01 AI113867NIAID NIH HHS UM1 AI144462
6 · The paper itselfAbstract
Applying cryoEM to small protein complexes is usually challenging due to their lack of features for particle alignment. Here, we characterized antibody responses to 21 kDa HIV membrane-proximal external region germline-targeting (MPER-GT) immunogens through cryoEM by complexing them with 10E8 or Fabs derived from MPER-GT immunized animals. Distinct antibody-antigen interactions were analyzed using atomic models generated from cryoEM maps. Mutagenesis screening revealed off-target mAbs that do not compete with 10E8 bind non-MPER epitopes, and the two most dominant epitopes were verified by cryoEM. The structures of 10E8-class on-target Fabs showed binding patterns that resemble the YxFW motif in the 10E8 HCDR3 loop. Additionally, we demonstrate that high-resolution maps can be generated from heterogeneous samples with pooled competing Fabs. Overall, our findings will facilitate the optimization of MPER GT-antigens and push the size limit for cryoEM-based epitope mapping with smaller antigens and heterogeneous antibody mixes.
Indexed as
cryoEMgermline-targetingHIV-1 Envmembrane-proximal external region (MPER)
Identifiers
PMID40894785
PMCPMC12393349
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