Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses.

Esther Blanco,David Andreu,Elisa Torres,Rodrigo Cañas-Arranz,Patricia De León,Mar Forner,María J Bustos,Francisco Sobrino,Sira Defaus

doi:10.3390/molecules26164714

Abstract

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.

Highlights

Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating animal disease [1–3] for which vaccination and strict regulations on animal movements and markets are the only means for control [4]
We previously showed that immunization of Swiss mice with B2 T elicits specific
T-cell epitope needs to be included in the same construct with the B-cell peptide to efficiently elicit FMD virus (FMDV) antibodies, groups of 10 mice were immunized and boosted with

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating animal disease [1–3] for which vaccination and strict regulations on animal movements and markets are the only means for control [4]. The current OIE-approved vaccines consist of the chemically inactivated whole virus emulsified with different adjuvants (reviewed in [5]). In an outbreak in regions where vaccination is not implemented, massive culling of susceptible animals has been the main measure to control the spread of the disease, leading to large economic losses as well as ethical controversy [6]. Conventional polyvalent FMDV vaccines, containing two or more inactivated viruses from different serotypes, aim to match the potentially circulating viruses and the epidemiological status of each region/country

Methods

Results

Conclusion