Foot-and-mouth disease: genomic and proteomic structure, antigenic sites, serotype relationships, immune evasion, recent vaccine development strategies, and future perspectives

Abstract

Foot-and-mouth disease (FMD) is a highly contagious and transmissible disease that can have significant economic and trade repercussions during outbreaks. In Egypt, despite efforts to mitigate FMD through mandatory immunization, the disease continues to pose a threat due to the high genetic variability and quasi-species nature of the FMD virus (FMDV). Vaccines have been crucial in preventing and managing FMD, and ongoing research focusses on developing next-generation vaccines that could provide universal protection against all FMDV serotypes. This review thoroughly examines the genetic structure of FMDV, including its polyprotein cleavage process and the roles of its structural and non-structural proteins in immune evasion. Additionally, it explores topics such as antigenic sites, specific mutations, and serotype relationships from Egypt and Ethiopia, as well as the structural changes in FMDV serotypes for vaccine development. The review also addresses the challenges associated with creating effective vaccines for controlling FMD, particularly focusing on the epitope-based vaccine. Overall, this review offers valuable insights for researchers seeking to develop effective strategies and vaccines for controlling FMD.

Keywords: Foot-and-mouth disease; antigenic sites; immune evasion; matching; peptide vaccines; vaccines.

Figure 1

FMDV genome structure, protein cleavage, and VP1 antigenic composition.

Figure 2

FMDV immune evasion strategies targeting host immune system. Key structural and non-structural proteins of FMDV, including VP1, VP2, VP3, L^pro, 2B, 2C, 3A, and 3C^Pro target various components of the host immune system. These proteins inhibit interferon (IFN) production, suppress innate immune signaling pathways, disrupt critical cellular processes, and evade immune recognition. These all facilitate viral replication and persistence in the host.

Figure 3

Graphic representation of the potential factors contributing to FMDV vaccine ineffectiveness.

Figure 4

Classification of foot-and-mouth disease virus (FMDV) vaccines by generation, showcasing the progression from traditional methods to advanced biotechnological approaches. The first generation (Classical) vaccine includes whole inactivated vaccines, which use chemical agents such as formaldehyde and beta-propiolactone or heat inactivation to eliminate viral infectivity, and live attenuated vaccines which are developed through genetic mutations, passaging, temperature sensitivity, reassortment, or chemical treatment to create a weakened virus that still elicits an immune response. The second generation (novel) vaccine introduces vector-based vaccines, utilizing viral vectors to deliver FMDV antigens effectively, and epitope-based vaccines, which employ synthesized peptides that mimic specific T-cell and B-cell epitopes to stimulate targeted immune responses. In the third generation (next generation) vaccine, further advancements are seen with plant transgenic vaccines, where transgenic plants are engineered to express FMDV antigens, DNA vaccines that use recombinant plasmids for gene delivery, and virus-like particles (VLPs), which are virus shells devoid of genetic material designed to mimic the virus structure and trigger a strong immune response. These generational advancements reflect improvements in vaccine safety, efficacy, and production efficiency, addressing the need for effective FMDV prevention strategies in livestock populations.

Figure 5

Different models of multiple-antigen peptide (MAP) systems. MAPs are dendritic polymers with lysine cores (represented as green circles) and multiple antigenic epitopes. The B4T model shows a lysine core with four B-cell epitopes connected to one T-cell epitope. The B2T model displays a simpler structure with two B-cell epitopes linked to one T-cell epitope. The B2T-TB2 model features a linear arrangement with two B-cell epitopes on each end, connected through lysine cores to central T-cell epitopes. The figure is based on [189] with modifications.