Genetic variation and evolution of foot–and–mouth disease virus serotype A in relation to vaccine matching

•The antigenic relationship of three anti-FMDV/A sera with field isolates was analyzed.•The IRQ/24/64, IRN/05, and ARG/01 sera showed different matches to the field isolates.•Together antigenic sites 1 and 3 contributed about 71% of the amino acid variations.•The substitutions at the antigenic sites influenced the vaccine matching results.•Genetic monitoring should include VP1, VP2, and VP3 for vaccine determination. Foot–and–mouth disease (FMD) is a severe, highly contagious viral disease that affects a wide variety of domestic and wild cloven-hoofed animals. FMD vaccines can play a vital role in disease control and are very widely used globally each year. However, due to the diversity of FMDV, the choice of FMD vaccine is still a huge challenge. In this study, 45 FMDV/A isolates were phylogenetically categorized into three topotypes: ASIA (n = 31), AFRICA (n = 10), and EURO–SA (n = 4). Three sera collected from vaccinated cattle with FMDV A22/IRQ/24/64, A/IRN/05, and A/ARG/01 were used to evaluate their antigenic relationship (r1) with the field isolates. The IRQ/24/64 serum demonstrated a 39% (17/44) match (r1 ≥ 0.3) to the field isolates, whereas IRN/05 serum and ARG/01serum showed an 18% (8/44) and a 2% (1/44) match (r1 ≥ 0.3) to the field isolates, respectively. The A22/IRQ/24/64 matched with isolates mainly from topotype ASIA, with limited cross–topotype match with isolates from topotypes AFRICA and EURO–SA. However, the A/IRN/05 did not show a cross–topotype match with topotype AFRICA isolates and A/ARG/01 failed to match any isolates from topotypes ASIA and AFRICA. After analyzing the amino acid variation of the known antigenic sites of 45 strains of FMDV/A, it was found that together antigenic sites 1 and 3 contributed about 71% of the amino acid changes to the vaccine evaluated. Based on the capsid sequences, the FMDV/A evolved unequally among topotypes. The topotypes of ASIA and AFRICA evolves faster than that of EURO–SA. The FMDV/A continues to show a high level of genetic diversity driven by a high substitution rate, purifying selection, and positive selection concentrated on antigenic sites or near antigenic sites. The current research shows the challenges of the FMDV/A vaccine selection and emphasizes the importance of continuous monitoring of antigenic evolution for the selection of effective vaccines.