ArticleImmunity2022
Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
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Who cites it
60 citing papers in PubMed, 75 citations in OpenAlex.
- Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.Science (New York, N.Y.) · 2025Trial
- Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses.PLoS biology · 2026Article
- Apex-guided HIV vaccination: liposome-displayed Env trimers elicit PG9-like cross-neutralizing antibodies.Signal transduction and targeted therapy · 2026Article
- Article
- Rapid boosting increases germinal center responses to sequential vaccines.Nature immunology · 2026Article
- Heavy-chain immune repertoire sequencing enables language-model prediction of antigen-specific antibodies.Research square · 2026Article
- Article
- 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
- Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques.Immunity · 2026Article
- Decoding epitope immunodominance in HIV Env using cryoEM and machine learning.bioRxiv : the preprint server for biology · 2026Article
- Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization.bioRxiv : the preprint server for biology · 2026Article
- Nanoparticle Immunoadjuvant Complexes Augment Germinal Center Responses to Vaccination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vaccine elicitation of HIV-1 neutralizing antibodies against both V2 apex and fusion peptide in rhesus macaques.Cell reports · 2026Article
- The buried S2 apex of SARS-CoV-2 spike elicits an immunodominant germline-restricted public antibody response.bioRxiv : the preprint server for biology · 2026Article
- Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.Science immunology · 2026Article
- Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.Science immunology · 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
- A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins for Vaccine Design.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
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Authors and funding
30 authors at 3 institutions in 2 countries.
Jordan R WillisCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Zachary T BerndsenCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Krystal M MaCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jon M SteichenCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Torben SchiffnerCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Elise LandaisCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Alessia LiguoriCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Oleksandr KalyuzhniyCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Sabyasachi BabooDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Oluwarotimi OmorodionCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jolene K DiedrichSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Xiaozhen HuCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Erik GeorgesonCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nicole PhelpsCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Saman EskandarzadehCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bettina GroschelCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Michael KubitzCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yumiko AdachiCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tina-Marie MullinCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nushin B AlaviCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Samantha FalconeModerna Inc., Cambridge, MA 02139, USA.
Sunny HimansuModerna Inc., Cambridge, MA 02139, USA.
Andrea CarfiModerna Inc., Cambridge, MA 02139, USA.
Ian A WilsonCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
John R YatesDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
James C PaulsonDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Andrew B WardCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
William R SchiefCenter for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: schief@scripps.edu.
Scripps Research Institute · USModerna Therapeutics (United States) · USUniversity of Southampton · GB
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
$201.6MSupport Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI GODZIK, ADAM · 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 SUSAN JANET LITTLE · 1994 to 2026
$78.4MGlycan dependent epitopes of HIV broadly neutralizing antibodiesR01AI113867 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C, SCHIEF, WILLIAM R. · 2014 to 2018
$4.8MNCATS NIH HHS UL1 TR001442NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI113867NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
Abstract
Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining region 3 (HCDR3), suggesting that the rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy-chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bound inferred germlines for PCT64 and PG9 and had higher affinities for bnAbs, determined cryo-EM structures of ApexGT trimers complexed with inferred-germline and bnAb forms of PCT64 and PG9, and developed an mRNA-encoded cell-surface ApexGT trimer. These methods and immunogens have promise to assist HIV vaccine development.
Indexed as
AIDS VaccinesHIV-1HIV InfectionsAntibodies, NeutralizingBroadly Neutralizing AntibodiesComplementarity Determining Regionsenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesHumansAIDS VaccinesAntibodies, NeutralizingBroadly Neutralizing AntibodiesComplementarity Determining Regionsenv Gene Products, Human Immunodeficiency VirusHIV AntibodiesAIDS vaccinesgermline targetingHIV antibodiesimmunoinformaticsstructural vaccinology
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