ArticleNPJ vaccines2024
Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.
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Article in NPJ vaccines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
13.7field-weighted citation impact, top 1% of its field
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.Science (New York, N.Y.) · 2025Trial
- Precise targeting of HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2025Trial
- Computational mining of B cell receptor repertoires reveals antigen-specific and convergent responses to Ebola vaccination.Frontiers in immunology · 2024Trial
- Article
- VRC01-CLASS PRECURSOR FREQUENCY IN AN AFRICAN POPULATION IS INFLUENCED BY IGHV1-2 ALLELIC COMPOSITION AND NOT MALARIA EXPOSURE.Research square · 2026Article
- Synthetic rewriting of the IGH locus.Cell genomics · 2026Article
- An integrated human immunoglobulin germline resource linking allele diversity to expressed repertoire structure.bioRxiv : the preprint server for biology · 2026Article
- Article
- DNA origami vaccines program antigen-focused germinal centers.Science (New York, N.Y.) · 2026Article
- Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity.Immunity · 2026Article
- Functional Convergence of Genetically Diverse B-Cell Receptors in Simian-HIV Infected Rhesus Macaques.bioRxiv : the preprint server for biology · 2026Article
- Necessity of individual VDJ-databases for annotating antibody heavy chain characteristics in non-human primates.Immunogenetics · 2025Article
- Germline polymorphisms in the immunoglobulin kappa and lambda loci underpinning antibody light chain repertoire variability.Nature communications · 2025Article
- Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy-chain locus.Genome research · 2025Article
- HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates.Science immunology · 2025Article
- Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Optimizing human B cell repertoire analyses to interpret clinical data and design sequential HIV vaccines.NPJ vaccines · 2025Article
- Germline-encoded recognition of peanut underlies development of convergent antibodies in humans.Science translational medicine · 2025Article
- ALIGaToR: A tool for the automated annotation of immunoglobulin and T cell receptor genomic loci.bioRxiv : the preprint server for biology · 2025Article
- Article
Corrections and comments
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Authors and funding
42 authors at 9 institutions in 3 countries.
Allan C deCamp *Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. adecamp@scharp.org.ORCID http://orcid.org/0000-0003-1404-4322
Martin M Corcoran *Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
William J Fulp *Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Jordan R WillisIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Christopher A CottrellIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-3364-3083
Daniel L V BaderIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Oleksandr KalyuzhniyIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-5273-1951
David J LeggatVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4019-7170
Kristen W CohenVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-8901-9941
Ollivier HyrienVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Sergey MenisIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Greg FinakVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0003-4341-9090
Lamar Ballweber-FlemingVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-6180-5545
Abhinaya SrikanthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jason R PlylerVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Farhad RahamanIAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
Angela LombardoIAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
Vincent PhiliponisIAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
Rachael E WhaleyVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Aaron SeeseVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-5877-6229
Joshua BrandVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4578-4860
Alexis M RuppelVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7391-1583
Wesley HoylandVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Celia R MahoneyVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Alberto CagigiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Alison TaylorVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2319-8481
David M BrownThe Foundation for the National Institutes of Health, North Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4463-8316
David R AmbrozakVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Troy SincombIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Tina-Marie MullenIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Janine MaenzaVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Orpheus KolokythasDepartment of Radiology, University of Washington, Seattle, WA, 98195, USA.
Nadia KhatiDepartment of Radiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.ORCID http://orcid.org/0000-0001-9198-9499
Jeffrey BethonyDepartment of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Mario RoedererVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-7448-7040
David DiemertDepartment of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.ORCID http://orcid.org/0000-0002-2789-0512
Richard A KoupVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Dagna S LauferIAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
Juliana M McElrathVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Adrian B McDermottVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0616-9117
Gunilla B Karlsson HedestamDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden. gunilla.karlsson.hedestam@ki.se.
William R SchiefIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA. schief@scripps.edu.ORCID http://orcid.org/0000-0002-1120-0150
National Institutes of Health · USFred Hutch Cancer Center · USScripps Research Institute · USInternational AIDS Vaccine Initiative · USGeorge Washington University · USKarolinska Institutet · SEUniversity of Washington · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAFoundation for the National Institutes of Health · US
Funding
LC: HIV Vaccine Trials NetworkUM1AI068618 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Margaret Juliana McElrath · 2011 to 2026
$483.6MSDMC: HIV Vaccine Trials NetworkUM1AI068635 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Peter B. Gilbert, Yunda Huang · 2011 to 2026
$385.9MIdentification 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
$201.6MSystems Biology CoreU19AI128914 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI Margaret Juliana McElrath, KENNETH D STUART · 2017 to 2026
$29.5MSeattle Vaccine Trials UnitUM1AI069481 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Rachel Ann Bender Ignacio, Margaret Juliana McElrath · 2012 to 2026
$24.4MStructure/function studies of immunogen recognition by anti-HIV antibody b12P01AI094419 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2011 to 2015
$10.6MNIAID NIH HHS P01 AI094419NIAID NIH HHS U19 AI128914NIAID NIH HHS UM1 AI068618NIAID NIH HHS UM1 AI068635NIAID NIH HHS UM1 AI069481NIAID NIH HHS UM1 AI144462
Abstract
Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.
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