Journal Article

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

Jakubowski, Aniela, Thuy, T. Le, Beckett, Kirrilee, Seenappa, Lochana M., Dasari, Vijayendra, McNeil, Lisa K., Khanna, Rajiv, Haqq, Christopher M., Panikkar, Archana, Ambalathingal, George, Palmer, Erica, Zhang, Jeff, Solomon, Matthew, Smith, Caitlyn, DeMuth, Peter C., Steinbuck, Martin P.

2023

Overview

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. There is a clinical need for effective and efficacious vaccines for Epstein-Barr virus (EBV) that induce substantive and protective immunity. Here the authors use a combined lymph-node targeted adjuvant and subunit vaccine against EBV and show the induction and effectiveness in a human leukocyte antigen expressing murine model.’

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 13/31 / 631/250/254 / 631/250/255/2514 / 631/250/590/2294 / 631/326/596/1553 / 64/60 / 82/1 / 82/80 / 82/83 / Animal models / Animals / Antigens / CD4 antigen / CD8 antigen / CD8-Positive T-Lymphocytes / Cell-mediated immunity / Combined vaccines / Epitopes / Epitopes, T-Lymphocyte / Epstein-Barr virus / Epstein-Barr Virus Infections - prevention & control / Glycoproteins / Herpesvirus 4, Human / Histocompatibility antigen HLA / Humanities and Social Sciences / Humoral immunity / Immunity / Immunization / Immunoglobulin G / Latent infection / Lymph Nodes / Lymphatic system / Lymphocytes / Lymphocytes B / Lymphocytes T / Mice / multidisciplinary / Multiple sclerosis / Science / Science (multidisciplinary) / Vaccines / Vaccines, Subunit / Viruses