Abstract:
Foot-and-mouth disease (FMD) continues to be a major burden for livestock owners in
endemic countries and a continuous threat to FMD-free countries. The epidemiology and
control of FMD in Africa is complicated by the presence of five clinically indistinguishable
serotypes. Of these the Southern African Territories (SAT) type 3 has received limited
attention, likely due to its restricted distribution and it being less frequently detected.
We investigated the intratypic genetic variation of the complete P1 capsid-coding region
of 22 SAT3 viruses and confirmed the geographical distribution of five of the six SAT3
topotypes. The antigenic cross-reactivity of 12 SAT3 viruses against reference antisera
was assessed by performing virus neutralization assays and calculating the r1-values,
which is a ratio of the heterologous neutralizing titer to the homologous neutralizing
titer. Interestingly, cross-reactivity between the SAT3 reference antisera and many SAT3
viruses was notably high (r1-values >0.3). Moreover, some of the SAT3 viruses reacted
more strongly to the reference sera compared to the homologous virus (r1-values >1). An
increase in the avidity of the reference antisera to the heterologous viruses could explain
some of the higher neutralization titers observed. Subsequently, we used the antigenic
variability data and corresponding genetic and structural data to predict naturally
occurring amino acid positions that correlate with antigenic changes. We identified four
unique residues within the VP1, VP2, and VP3 proteins, associated with a change in
cross-reactivity, with two sites that change simultaneously. The analysis of antigenic
variation in the context of sequence differences is critical for both surveillance-informed
selection of effective vaccines and the rational design of vaccine antigens tailored for
specific geographic localities, using reverse genetics.
