Abstract:
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. An
outbreak of FMD not only severely decreases livestock productivity, but also impacts on both
the local and export trade of susceptible animals and their products. This, in turn, negatively
impacts the economy of affected countries. Of the seven serotypes that exist for FMD virus
(FMDV), the three South African Territories (SAT) types display greater intratypic genomic
and antigenic variation than the traditional “Euro-Asian” types. Although antigenic variation
represents an important adaptive strategy of FMDV, especially in its maintenance host, it
contributes to the decrease of vaccine cross-protection in the field, thus rendering available
vaccines less effective. Knowledge of the amino acid residues that comprise the antigenic
determinants will allow for the structural design of vaccine seed viruses that may provide
improved protection against specific outbreak strains.
The SAT2 type viruses, which are responsible for most of the FMD outbreaks in domestic
animals in southern Africa, are the most variable of the SAT serotypes. In order to identify
antigenic regions present on a SAT2 FMDV, two approaches were followed. In the first
approach, a SAT2 vaccine strain, ZIM/7/83, was panned with a naïve chicken phagedisplayed
library. Three unique SAT2/ZIM/7/83-specific phage-scFvs were obtained. Of
these, phage-scFv2 was able to neutralize the SAT2/ZIM/7/83 virus and following sequencing
of neutralization-resistant virus variants, an antigenic site was mapped to include residue 159
of the VP1 capsid protein. In the second approach, genetically modified viruses were
generated in which known and predicted epitopes of SAT2/ZIM/7/83 were replaced with
those of a disparate virus, SAT2/KNP/19/89, to determine the role of known SAT2 epitopes
and to identify new potential antigenic regions. Following characterization of the epitopereplaced
mutant viruses and studies with SAT2-specific monoclonal antibodies, two
additional antigenic sites were mapped to include residues 71-72 of the VP2 capsid protein.
The information gained from this study will not only increase the knowledge of the antigenic
sites of SAT2 viruses and aid in identifying more suitable vaccine strains for SAT2 viruses,
but is also the first step towards the production of a SAT2-specific epitope-based vaccine.
