Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health

Abstract

Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, e.g., to cold chain transport, handling and storage. In this context, subunit vaccines where the essential antigenic traits (but not the entire pathogen) are presented in rationally designed fashion have emerged as an attractive alternative to conventional ones. In particular, this includes the option of fully synthetic peptide vaccines able to mimic well-defined B- and T-cell epitopes from the infectious agent and to induce protection against it. Although, in general, linear peptides have been associated to low immunogenicity and partial protection, there are several strategies to address such issues. In this review, we report the progress towards the development of peptide-based vaccines against foot-and-mouth disease (FMD) a highly transmissible, economically devastating animal disease. Starting from preliminary experiments using single linear B-cell epitopes, recent research has led to more complex and successful second-generation vaccines featuring peptide dendrimers containing multiple copies of B- and T-cell epitopes against FMD virus or classical swine fever virus (CSFV). The usefulness of this strategy to prevent other animal and human diseases is discussed.

Keywords: FMDV; epitope-based vaccines; peptide; vaccines; veterinary medicine.

Figure 1

Animal Diseases, Infections and Infestations: (a) Counts of terrestrial and aquatic animal diseases published at OIE’s 2020 infectious diseases list; (b) Causative agent of the animal diseases reported in absolute values; (c) Prevention and control treatments in animal diseases reported in percentage values.

Figure 2

General scheme of (a) B-cell epitope recognition through: (1) linear (continuous residues); and (2) conformational (discontinuous residues) B-cell epitopes from antigens binding B-cell receptor (BCR) immunoglobulins displayed on the surface of/attached to B-cells; (b) T-cell epitope recognition by peptides derived from antigens presented via major histocompatibility complex (MHC) I and II molecules bound to APCs and recognized by (3) CD8+ and (4) CD4+ T-cells T cell receptors (TCR), respectively. Adapted from [28,29].

Figure 3

Schematic representation of the adaptive immune response induced by FMDV. APCs present viral peptides (T-cell epitopes) via MHC class I and II molecules to CD8+ and CD4+ T-lymphocytes, respectively. CD4+ T-cells can (i) cooperate with activated B-lymphocytes to produce nAbs; and (ii) interact with CD8+ T-lymphocytes that are previously activated by association with MHC class I molecules on the surface of infected cells, to trigger a cytotoxic (CTL) response.

Figure 4

Overview of two synthetic peptides mimicking discontinuous site D of FMDV serotype C using (a) a cross-sectional view of the critical residues, with the VP2 and VP3 fragments containing them linked by means of a polyproline helix, and the VP1 segment attached to the VP3 one by a disulfide bond [116]; (b) a front view that favors display of surface-exposed antigenic residues [117]. The five critical residues of discontinuous site D are labeled by an asterisk (*) and non-native residues are in yellow. Adapted from [116,117].

Figure 5

(a) Branching N^α and N^ε amino groups forming the Lys core of a MAP construct; (b) Different dendrimer multiplicities starting from a Lys core. Each circle represents a Lys residue, each line a peptide sequence and the colors denote the level of multiplicity.

Figure 6

Synthetic scheme of the B₂T vaccine prototype against FMDV.

Figure 7

Synthetic scheme of B₂T-TB₂ vaccine prototype against FMDV.