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

淋巴结靶向多表位亚单位疫苗可促进表达HLA的小鼠对EB病毒的有效免疫。

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作者: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 # ,Rajiv Khanna #

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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