ArticleCell host & microbe2024
Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.
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Article in Cell host & microbe, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
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23 citing papers in PubMed, 27 citations in OpenAlex.
- 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
- What Antibody Repertoires See: Structural and Immunogenetic Insights Into Influenza A Virus Hemagglutinin Recognition.Immunological reviews · 2026Review
- 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
- Charting the Path Forward for HIV Immune-Based Prevention: Contributions of the Division of AIDS at NIAID.Vaccines · 2026Article
- Decoding the glycan shield: Immune recognition and response to the HIV-1 envelope trimer.The Journal of biological chemistry · 2026Review
- Recurrent SARS-CoV-2 Omicron broadly neutralizing humanized antibodies in different single human VProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Humoral epitope dominance and immune imprinting by SARS-CoV-1 and SARS-CoV-2 vaccines.Immunology and cell biology · 2026Article
- Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Functional Convergence of Genetically Diverse B-Cell Receptors in Simian-HIV Infected Rhesus Macaques.bioRxiv : the preprint server for biology · 2026Article
- Germline-Targeting Strategies to Induce bNAbs against HIV-1.Current HIV research · 2026Review
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Article
- Efforts toward achieving the goal of ending AIDS by 2030: from antiretroviral drugs to HIV vaccine and cure research.Science China. Life sciences · 2025Article
- Status of HIV vaccine development: progress and promise.Journal of the International AIDS Society · 2025Article
- An engineered immunogen activates diverse HIV broadly neutralizing antibody precursors and promotes acquisition of improbable mutations.Science translational medicine · 2025Article
- Understanding the performance of HIV-1 viral vector vaccines: adenovirus and poxvirus case studies.Frontiers in immunology · 2025Review
- Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.Nature communications · 2024Article
- Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.Journal of virology · 2024Article
- Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1.Journal of biomedical science · 2024Review
- Cryo-electron microscopy in the study of virus entry and infection.Frontiers in molecular biosciences · 2024Review
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Authors and funding
35 authors at 7 institutions in 2 countries.
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.wiehe@duke.edu.
Kevin O SaundersDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Microbiology and Molecular Genetics, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.saunders@duke.edu.
Victoria StallsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Derek W CainDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Sravani VenkatayogiDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Joshua S Martin BeemDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Madison BerryDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Tyler EvangelousDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Rory HendersonDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Bhavna HoraDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Shi-Mao XiaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Chuancang JiangDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Amanda NewmanDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Cindy BowmanDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Xiaozhi LuDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Mary E BryanDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Joena BalDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Aja SanzoneDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Haiyan ChenDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Amanda EatonDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Mark A TomaiCorporate Research Materials Lab, 3M Company, St. Paul, MN 55144, USA.
Christopher B FoxAccess to Advanced Health Institute, Seattle, WA 98102, USA.
Ying K TamAcuitas, Inc, Vancouver, BC, Canada.
Christopher BarbosaAcuitas, Inc, Vancouver, BC, Canada.
Mattia BonsignoriTranslational Immunobiology Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hiromi MuramatsuDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
S Munir AlamDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
David C MontefioriDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Wilton B WilliamsDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
Norbert PardiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ming TianBoston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Drew WeissmanDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Frederick W AltBoston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Priyamvada AcharyaDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@dm.duke.edu.
Duke University · USUniversity of Pennsylvania · USAcuitas Therapeutics (Canada) · CABoston Children's Hospital · US3M (United States) · USAccess to Wholistic and Productive Living Institute · USNational Institutes of Health · US
Funding
Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2012 to 2018
$204.7MNonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4MVirus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7MProject 2: Current Good Manufacture Practices (CGMP) Production of Nucleoside-Modified mRNAs Encoding HIV-1 EnvelopesU19AI135902 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2018 to 2022
$19.8MOrigin and maturation of protective memory B cell responses against pathogenic viruses in natural infections and upon vaccination.ZIAAI001342 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BONSIGNORI, MATTIA · 2021 to 2025
$7.0MNIAID NIH HHS P01 AI131251NIAID NIH HHS U19 AI135902NIAID NIH HHS UM1 AI100645NIAID NIH HHS UM1 AI144371
Abstract
A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof of concept and milestone toward development of an HIV-1 vaccine.
Indexed as
AIDS VaccinesAntibodies, NeutralizingB-LymphocytesHIV-1HIV AntibodiesAnimalsBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV InfectionsHumansImmunization, SecondaryMiceMutationVaccine DevelopmentAIDS VaccinesAntibodies, NeutralizingBroadly Neutralizing Antibodiesenv Gene Products, Human Immunodeficiency VirusHIV Antibodiesaffinity maturationB cell developmentbroadly neutralizing antibodiesHIV vaccineimprobable mutationsmRNA vaccinevaccine design
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