ArticleNature communications2021
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61citing papers in PubMed
7.9field-weighted citation impact, top 1% of its field
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Who cites it
61 citing papers in PubMed, 78 citations in OpenAlex.
- Precise targeting of HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2025Trial
- Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial.Science translational medicine · 2025Trial
- Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.Cell reports · 2025Trial
- Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies.The Journal of experimental medicine · 2024Trial
- HIV-1 BG505 SOSIP immunization induced B cell expansion targeting the 465-glycan hole, with neutralizing antibodies exhibiting distinct binding modes and mechanisms of virus inhibition.PLoS pathogens · 2026Article
- Deep mining of the human antibody repertoire identifies frequent and genetically diverse CDRH3 topologies targetable by vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Differential contributions of human oligosaccharyltransferase complexes OST-A and OST-B to HIV-1 envelope glycoprotein glycosylation.Journal of virology · 2026Article
- Decoding epitope immunodominance in HIV Env using cryoEM and machine learning.bioRxiv : the preprint server for biology · 2026Article
- Polyclonal Antibody Therapeutics: Analytical Innovations and Regulatory Perspectives for Addressing Heterogeneity Challenges.Analytical chemistry · 2026Review
- The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.bioRxiv : the preprint server for biology · 2026Article
- Virus glycoprotein nanodisc platform for vaccine analytics.Nature communications · 2026Article
- Cryo-EM structures of antibodies elicited by germline-targeting HIV MPER epitope scaffolds.Cell reports · 2026Article
- Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development.Current HIV research · 2026Review
- Rational design of flavivirus E protein vaccine optimizes immunogenicity and mitigates antibody dependent enhancement risk.Nature communications · 2025Article
- Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody-viral glycoprotein complexes.Nature biomedical engineering · 2025Article
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.NPJ vaccines · 2025Article
- Functional and epitope specific monoclonal antibody discovery directly from immune sera using cryo-EM.Science advances · 2025Article
- Structural elucidation of full-length Pfs48/45 in complex with potent monoclonal antibodies isolated from a naturally exposed individual.Nature structural & molecular biology · 2025Article
- Fusion of Complement Fragment C3d Enhances Germinal Center Responses to HIV-1 Envelope Glycoproteins.bioRxiv : the preprint server for biology · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 8 institutions in 3 countries.
Aleksandar AntanasijevicDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Leigh M SewallDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Christopher A CottrellDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-3364-3083
Diane G CarnathanDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Luis E JimenezDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Julia T NgoDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Jennifer B SilvermanDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.ORCID 0000-0001-8933-8638
Bettina GroschelDepartment 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.ORCID 0000-0001-5137-4625
Jinal BhimanDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Raiza BastidasDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Celia LaBrancheDepartment of Surgery, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0002-6653-6655
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID 0000-0003-2547-968X
Jeffrey CoppsDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0003-4793-7258
Hailee R PerrettDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-1326-1731
Kimmo RantalainenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-3158-9183
Fabien CannacDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Yuhe R YangDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Alba Torrents de la PeñaDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Rebeca Froes RochaDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Zachary T BerndsenDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
David BakerInstitute for Protein Design, Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7896-6217
Neil P KingInstitute for Protein Design, Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID 0000-0002-2978-4692
Rogier W SandersAcademic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands.
John P MooreWeill Cornell Medicine, Cornell University, New York, NY, USA.ORCID 0000-0002-9902-6096
Shane CrottyLa Jolla Institute for Immunology, La Jolla, CA, USA.ORCID 0000-0002-6484-6262
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID 0000-0002-1072-2694
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, NC, USA.
Dennis R BurtonInternational AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-6711-9864
William R SchiefInternational AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-1120-0150
Guido SilvestriDivision of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Andrew B WardDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. andrew@scripps.edu.ORCID 0000-0001-7153-3769
Scripps Research Institute · USEmory University · USCornell University · USDuke Medical Center · USUniversity of Southampton · GBHoward Hughes Medical Institute · USLa Jolla Institute for Immunology · USUniversity of Washington · US
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
$201.6MYerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0MSupport Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MCELRATH, MARGARET JULIANA · 2012 to 2018
$131.5MUC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3MVirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Mitchell Smith · 1994 to 2026
$78.4MStructural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4MViral Testing Core-Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research CenterU42OD011023 · OD · EMORY UNIVERSITY · PI Matthew Ryan Gardner · 2018 to 2026
$17.5MDissecting Polyclonal Sera to Reveal Correlates of Productive Immune Responses to HIVR01AI136621 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Lars Oliver Hangartner, Andrew Barrett Ward · 2018 to 2026
$8.0MBroadening autologous Tier 2 anti-HIV neutralizing antibodiesF31AI131873 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI COTTRELL, CHRISTOPHER ANDREW · 2017 to 2020
$95kHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR001442NIAID NIH HHS F31 AI131873NIAID NIH HHS P01 AI110657NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI136621NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462NIH HHS P51 OD011132NIH HHS U42 OD011023
Abstract
Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.
Indexed as
AIDS VaccinesAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibody FormationCryoelectron Microscopyenv Gene Products, Human Immunodeficiency VirusEpitopesGlycosylationHIV-1HIV AntibodiesHIV InfectionsHumansMacaca mulattaModels, MolecularProtein ConformationAIDS VaccinesAntibodies, MonoclonalAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV Antibodies
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