Antigenic variation of foot-and-mouth disease virus serotype A

Abstract

The current measures to control foot-and-mouth disease (FMD) include vaccination, movement control and slaughter of infected or susceptible animals. One of the difficulties in controlling FMD by vaccination arises due to the substantial diversity found among the seven serotypes of FMD virus (FMDV) and the strains within these serotypes. Therefore, vaccination using a single vaccine strain may not fully cross-protect against all strains within that serotype, and therefore selection of appropriate vaccines requires serological comparison of the field virus and potential vaccine viruses using relationship coefficients (r1 values). Limitations of this approach are that antigenic relationships among field viruses are not addressed, as comparisons are only with potential vaccine virus. Furthermore, inherent variation among vaccine sera may impair reproducibility of one-way relationship scores. Here, we used antigenic cartography to quantify and visualize the antigenic relationships among FMD serotype A viruses, aiming to improve the understanding of FMDV antigenic evolution and the scope and reliability of vaccine matching. Our results suggest that predicting antigenic difference using genetic sequence alone or by geographical location is not currently reliable. We found co-circulating lineages in one region that were genetically similar but antigenically distinct. Nevertheless, by comparing antigenic distances measured from the antigenic maps with the full capsid (P1) sequence, we identified a specific amino acid substitution associated with an antigenic mismatch among field viruses and a commonly used prototype vaccine strain, A22/IRQ/24/64.

Fig. 1.

Unrooted ML tree of 40 full P1 capsid nucleotide sequences using GTR+G+I in mega 5.10. Bootstrap replicates (1000) were performed, and only bootstrap values above 70 % are shown. The three different topotypes have been coloured: Asia (blue), Africa (purple) and Europe/South America (EURO-SA; green). *** indicates viruses that contained a proline at position 149. Bar, nucleotide substitutions per site.

Fig. 2.

Three-dimensional antigenic maps of the 46 FMDV serotype A viruses representing the global diversity of serotype A FMDV. Viruses (spheres) and antisera (open cubes) were positioned such that the distance from each serum to each virus is determined by the neutralization titre. Multidimensional scaling was used to position both sera and viruses relative to each other, so orientation of the map within the axes is free. Bar, 1 AU (equivalent to a twofold dilution in antibody titre). All views are shown at a different orientation to highlight the patterns seen (viewed using Pymol; DeLano Scientific LLC). (a) Viruses coloured according to different topotypes: Africa (red), Asia, (blue) and Europe/South America (green). (b) Viruses coloured to highlight the A/ASIA/Iran-05 lineage (green). (c) Viruses coloured by year: up to and including 2003 (blue), 2004 (turquoise), 2005 (light blue), 2006 (green), 2007 (dark green), 2008 (orange) and 2009 (red).

Fig. 3.

Pair-wise antigenic and genetic distance (P1) between viruses. The antigenic distances were derived from the three-dimensional antigenic map of FMDV serotype A. Pearson’s correlation coefficient was 0.42 (95 % CI is 0.36–0.48; P<2.2×10⁻¹⁶). The Spearmans’s rank correlation (ρ) was equal to 43 %.

Fig. 4.

Three-dimensional antigenic map of FMDV serotype A isolates (see Fig. 2). Viruses are coloured by amino acid at position 149: proline (red), A/IRQ/24/64 (orange), others (blue), not sequenced due to confidentiality agreement (white). The cubes indicate the different sera.

Fig. 5.

Boxplot of 166 r ₁ values obtained from the WRL/EURL for FMD against A₂₂/IRQ/24/64 vaccine virus. The amino acid at position 149 of VP1 and the resulting r ₁ value are shown. An r ₁ value ≥0.3 is suggestive of a vaccine match against A₂₂/IRQ/24/64 (horizontal line).