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

Vijayendra Dasari(QIMR Berghofer Medical Research Institute), Lisa K. McNeil(Intarcia Therapeutics (United States)), Kirrilee Beckett(QIMR Berghofer Medical Research Institute), Matthew D. Solomon(QIMR Berghofer Medical Research Institute), George Ambalathingal(QIMR Berghofer Medical Research Institute), T. Le Thuy(QIMR Berghofer Medical Research Institute), Archana Panikkar(QIMR Berghofer Medical Research Institute), Caitlyn Smith(QIMR Berghofer Medical Research Institute), Martin P. Steinbuck(Intarcia Therapeutics (United States)), Aniela Jakubowski(Intarcia Therapeutics (United States)), Lochana M. Seenappa(Intarcia Therapeutics (United States)), Erica Palmer(Intarcia Therapeutics (United States)), Jeff Zhang(Intarcia Therapeutics (United States)), Christopher M. Haqq(Intarcia Therapeutics (United States)), Peter C. DeMuth(Intarcia Therapeutics (United States)), Rajiv Khanna(QIMR Berghofer Medical Research Institute)
Nature Communications
August 8, 2023
Cited by 57Open Access
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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.


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