ArticleImmunity2025
Diverse priming outcomes under conditions of very rare precursor B cells.
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Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed.
- Article
- Rapid boosting increases germinal center responses to sequential vaccines.Nature immunology · 2026Article
- Atomic layer deposition for core-shell microparticle vaccines enabling programmable antigen delivery to lymph nodes enhance humoral immune responses.bioRxiv : the preprint server for biology · 2026Article
- Immunological memory to vaccines.Immunity · 2026Review
- Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading.Immunity · 2026Article
- Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization.bioRxiv : the preprint server for biology · 2026Article
- Atomic Layering Thermostable Antigen and Adjuvant (ALTAbioRxiv : the preprint server for biology · 2026Article
- Article
- Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025Article
- Simultaneous induction of multiple classes of broadly neutralizing antibody precursors by combination germline-targeting immunization in nonhuman primates.Science immunology · 2025Article
- Scale-up and cGMP manufacturing of next-generation vaccine adjuvant saponin/MPLA nanoParticles (SMNP).Journal of pharmaceutical sciences · 2025Article
- Clonal expansion and diversification of germinal center and memory B cell responses to booster immunization in primates.Cell reports · 2025Article
- Vaccination with an mRNA-encoded membrane-bound HIV envelope trimer induces neutralizing antibodies in animal models.Science translational medicine · 2025Article
- Clonal Expansion and Diversification of Germinal Center and Memory B Cell Responses to Booster Immunization in Primates.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
45 authors.
Patrick J MaddenLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Ester Marina-ZárateLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Kristen A RodriguesKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jon M SteichenConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Monolina ShilLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Kaiyuan NiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Katarzyna Kaczmarek MichaelsKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Laura MaiorinoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Amit A UpadhyayEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, USA.
Swati SahaDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Arpan PradhanEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Oleksandr KalyuzhinyConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
Alessia LiguoriConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
Paul G LopezLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Ivy PhungLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
Claudia FlynnIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
Amelia ZhouIAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
Mariane B MeloDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Ashley LemniosDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nicole PhelpsConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Erik GeorgesonConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nushin AlaviConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Michael KubitzConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Danny LuConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Saman EskandarzadehConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Amanda MetzEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, USA.
Oscar L RodriguezDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Kaitlyn ShieldsDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Steven SchultzeDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Melissa L SmithDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Brandon S HealyEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Deuk LimEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Vanessa R LewisEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Elana Ben-AkivaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
William PinneyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Justin GregoryKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Shuhao XiaoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Diane G CarnathanEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Sudhir Pai KasturiEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Corey T WatsonDepartment of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
Steven E BosingerEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, USA.
Guido SilvestriEmory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
William R SchiefConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA; Moderna, Inc., Cambridge, MA, USA.
Darrell J IrvineConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: djirvine@scripps.edu.
Shane CrottyLa Jolla Institute for Immunology, La Jolla, CA, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA, USA. Electronic address: shane@lji.org.
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
$167.0MPopulation genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding coloniesR24AI162317 · NIAID · EMORY UNIVERSITY · PI Steven Edward Bosinger, Corey Taylor Watson · 2021 to 2026
$5.5MMaximizing germinal centers and somatic hypermutation to HIV Env immunogensR37AI125068 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI Shane P Crotty, Darrell J Irvine · 2021 to 2026
$5.4MNovel nanoparticulate adjuvants to enhance HIV-1 Env specific mucosal antibody responsesR01AI145640 · NIAID · EMORY UNIVERSITY · PI KASTURI, SUDHIR PAI · 2019 to 2023
$5.0MKentucky Network for Innovation & Commercialization (“KYNETIC”)U01HL152392 · NHLBI · UNIVERSITY OF KENTUCKY · PI DWOSKIN, LINDA P, MERTEN, KEVYN E · 2019 to 2022
$3.9MIllumina NovaSeq 6000 High Throughput DNA Sequencer for Emory UniversityS10OD026799 · OD · EMORY UNIVERSITY · PI BOSINGER, STEVEN EDWARD · 2019 to 2019
$985kNovaSeq5000 High Throughput SequencerS10OD025052 · OD · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI SEUMOIS, GREGORY · 2018 to 2018
$832kHoward Hughes Medical InstituteNHLBI NIH HHS U01 HL152392NIAID NIH HHS R01 AI145640NIAID NIH HHS R24 AI162317NIAID NIH HHS R37 AI125068NIAID NIH HHS UM1 AI144462NIH HHS P51 OD011132NIH HHS S10 OD025052NIH HHS S10 OD026799
Abstract
Rare naive B cells have special pathogen-recognition features that enable outsized contributions to protective immunity but infrequently participate in immune responses. We investigatee how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (<1-in-50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs) compared with other conditions. All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP but scarce BG18-like B cells. Following homologous boosting, BG18-like memory B cells were present in a bolus priming group but with lower somatic hypermutation and affinities than ED+SMNP. This outcome inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses. Thus, antigen and inflammatory stimuli extensively impact priming and affinity maturation of rare B cells.
Indexed as
AIDS VaccinesHIV-1HIV InfectionsMemory B CellsPrecursor Cells, B-LymphoidAdjuvants, ImmunologicAnimalsAntibodies, NeutralizingGerminal CenterHIV AntibodiesHumansImmunologic MemoryMacaca mulattaSaponinsAdjuvants, ImmunologicAIDS VaccinesAntibodies, NeutralizingHIV AntibodiesSaponinsadjuvantsBG18bnAb precursorsescalating dosegermline-targetingHIV bnAbsHIV vaccinesnaive B cells
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