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Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice

Author

Listed:
  • Vijayendra Dasari

    (Berghofer Medical Research Institute)

  • Lisa K. McNeil

    (Elicio Therapeutics, Inc)

  • Kirrilee Beckett

    (Berghofer Medical Research Institute)

  • Matthew Solomon

    (Berghofer Medical Research Institute)

  • George Ambalathingal

    (Berghofer Medical Research Institute)

  • T. Le Thuy

    (Berghofer Medical Research Institute)

  • Archana Panikkar

    (Berghofer Medical Research Institute)

  • Caitlyn Smith

    (Berghofer Medical Research Institute)

  • Martin P. Steinbuck

    (Elicio Therapeutics, Inc)

  • Aniela Jakubowski

    (Elicio Therapeutics, Inc)

  • Lochana M. Seenappa

    (Elicio Therapeutics, Inc)

  • Erica Palmer

    (Elicio Therapeutics, Inc)

  • Jeff Zhang

    (Elicio Therapeutics, Inc)

  • Christopher M. Haqq

    (Elicio Therapeutics, Inc)

  • Peter C. DeMuth

    (Elicio Therapeutics, Inc)

  • Rajiv Khanna

    (Berghofer Medical Research Institute)

Abstract

The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8+ T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350-specific CD4+ T cells and EBV-specific CD8+ T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.

Suggested Citation

  • Vijayendra Dasari & Lisa K. McNeil & Kirrilee Beckett & Matthew Solomon & George Ambalathingal & T. Le Thuy & Archana Panikkar & Caitlyn Smith & Martin P. Steinbuck & Aniela Jakubowski & Lochana M. Se, 2023. "Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39770-1
    DOI: 10.1038/s41467-023-39770-1
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    References listed on IDEAS

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    1. Tobias V. Lanz & R. Camille Brewer & Peggy P. Ho & Jae-Seung Moon & Kevin M. Jude & Daniel Fernandez & Ricardo A. Fernandes & Alejandro M. Gomez & Gabriel-Stefan Nadj & Christopher M. Bartley & Ryan D, 2022. "Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM," Nature, Nature, vol. 603(7900), pages 321-327, March.
    2. Adam E Handel & Alexander J Williamson & Giulio Disanto & Lahiru Handunnetthi & Gavin Giovannoni & Sreeram V Ramagopalan, 2010. "An Updated Meta-Analysis of Risk of Multiple Sclerosis following Infectious Mononucleosis," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-5, September.
    3. Haipeng Liu & Kelly D. Moynihan & Yiran Zheng & Gregory L. Szeto & Adrienne V. Li & Bonnie Huang & Debra S. Van Egeren & Clara Park & Darrell J. Irvine, 2014. "Structure-based programming of lymph-node targeting in molecular vaccines," Nature, Nature, vol. 507(7493), pages 519-522, March.
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