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

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. Seenappa, Erica Palmer, Jeff Zhang, Christopher M. Haqq, Peter C. DeMuth and Rajiv Khanna ()
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39770-1

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