Contact: Pamela Opperman (PhD), Senior
Foot and mouth disease (FMD), of which FMD virus (FMDV) is the causative agent, is a contagious viral disease that affects cloven hoofed animals such as cattle, pigs, sheep, goats, and other artiodactyl species. FMD ranks as one of the most economically important infectious diseases of animals according to the World Organisation for Animal Health (OIE). Typical symptoms are vesicles and ulcers on the tongue and hooves, hence the name of the disease. Not only does this cause much discomfort and secondary infections, but also fever and occasional mortality especially among young animals.
The epidemiology of FMD in Africa is influenced by two different patterns, i.e. a cycle involving wildlife, in particular the African buffalo (Syncerus caffer), and an independent cycle maintained within livestock. Another unique feature of FMD epidemiology in Africa is the presence of at least five of the seven serotypes of FMD viruses (Southern African Territories [SAT] 1, SAT2, SAT3, A, and O), with the exception of types C and Asia-1. The presence of large numbers of African buffalo provides a potential source of sporadic infection to domestic livestock and other wildlife species. Although the precise mechanism of transmission of FMD from buffalo to cattle is not well understood, it's facilitated by direct contact between these two species. Once cattle are infected, they may maintain SAT infections without the further involvement of buffalo. Due to underreporting of FMD, the current strains circulating throughout sub-Saharan Africa are in many cases unknown.
Diseases caused by RNA viruses, like FMDV, are often difficult to control because of the high mutation rate and the continual emergence of novel genetic and antigenic variants that allow escape from the host's immune system. The implication of the antigenic variation is that the degree to which immunity induced by one virus is effective against another is largely dependent on the antigenic differences between them. Typically, an FMD vaccine will comprise a separate component for each serotype against which it needs to protect, as a combination vaccine.
Effective control and prevention of FMD relies largely on the implementation of strategies such as physical separation of wildlife and livestock, repeated vaccination of cattle herds exposed to wildlife, control of animal movements, and careful assessment of the risk of FMDV introduction into disease-free areas. The current inactivated vaccines have proven effective in reducing clinical disease in FMD-endemic areas and have been critical to the success of FMD control programs in South America and Europe. In Africa, the diversity of circulating field strains of FMDV makes the selection of sufficiently cross-protective FMD vaccines a challenge. Therefore, the success of any FMD control campaign ultimately depends on the abundant supply of vaccine of the appropriate strain composition and proven potency, adequate vaccine coverage, rapid vaccine development, overall planning and management by a well-resourced veterinary service, and the involvement and co-operation of the livestock farmer.
Current areas of research being explored at the ARC FMD research division are focused on the requirements of FMD diagnostics and vaccine production. For Southern Africa, emphasis is placed on FMD control thus research projects involve the improvement of diagnostic assays and FMDV vaccines. Using phage display technology, naïve and immune libraries are used to identify FMDV specific monoclonal antibodies, which are investigated for their use in diagnostic ELISAs to improve sensitivity and specificity. In addition, phage display is being utilised to identify FMDV epitopes. This knowledge, together with the research investigations on improving FMDV stability and cell culture adaptation, recombinant technology can be utilised to develop FMDV vaccines using reverse genetics. The aim of such vaccine research is to develop cost-effective and stable vaccines as well as vaccines with an extended antigenic coverage offering a broad immunological response. In addition, research focuses to understand FMDV in the Southern African perspective by investigating antigenic variation, transmission, pathogenesis, immune responses and persistence. Much research has been focused on FMDV in cattle and buffalo but the effect of other cloven-hoofed species on FMD control is apparent. Therefore, other areas of interest are the use and effectiveness of the FMD vaccine in goats as well as the validation of the FMD diagnostic assays for other small ruminants.
Melanie Chitray (PhD)
Tshifhiwa Nefefe (PhD)
Mabotse Tjale (PhD)
Maake L, Harvey W, Rotherham L, Opperman P, Theron J, Reeve R, Maree F. Genetic basis of antigenic variation of SAT3 foot-and-mouth disease virus. 2020. Frontiers in Veterinary Science 7: 568 DOI: 10.3389/fvets.2020.00568
Chitray M, Kotecha A, Nsamba P, Ren J, Maree S, Ramulongo T, Paul K.G, Theron J, Fry E.E, Stuart D.I, Maree, F.F. 2020. Symmetrical arrangement of positively charged residues around the 5-fold axes of SAT type foot-and-mouth disease virus enhances cell culture of field viruses. PLoS Pathogens 16(9):e1008828.
Lazarus D, Peta F, Blight D, Van Heerden J, Mutowembwa P, Heath L, Blignaut B, Opperman P, Fosgate G. Efficacy of a foot-and-mouth disease vaccine against a heterologous SAT1 virus challenge in goats. 2020. Vaccine 24: 4006-4015.
Chitray M, Opperman PA, Rotherham L, Fehrsen J, van Wyngaardt W, Frischmuth J, Rieder E, Maree F. Diagnostic and epitope mapping potential of single-chain antibody fragments against foot-and-mouth disease virus serotypes A, SAT1 and SAT3. 2020. Frontiers in Veterinary Science. DOI: 10.3389/fvets.2020.00475.
Maree F, Ramulongo T, Scott K, Opperman P, Mutomwemba P, Theron J. Pathogenesis, biophysical stability and phenotypic variance of SAT2 foot-and-mouth disease virus. 2020. Veterinary Microbiology 243, 108614.
Chitray M, Grazioli S, Willems T, Tshabalala T, De Vleeschauwerd A, Esterhuysen JJ, Brocchi E, De Clercq , Maree FF. The development and evaluation of a SAT-specific 3ABC DIVA test for Foot-and-mouth disease virus in the Southern Africa context. (2018). J. Virol Methods (255) 44-51.
Scott KA, Kotecha A, Seago J, Ren J, Fry EE, Stuart D, Charleston B, Maree FF. (2017) SAT2 foot-and-mouth disease virus (FMDV) structurally modified for increased thermostability. J. Virol. 91(10). pii: e02312-16. doi: 10.1128/JVI.02312-16.
Scott KA, Rathogwa NM, Capozzo AV, Maree FF. (2017) Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle. Vaccine 40: 5426-5433. Doi: 10.1016/j.vaccine.2017.02.003.
Reeve R, Borley DW, Maree FF, Upadhyaya S, Lukhwareni A, Esterhuysen JJ, Harvey WT, Blignaut B, Fry EE, Parida S, Paton DJ, Mahapatra M. (2016) Tracking the Antigenic Evolution of Foot-and-Mouth Disease Virus. PLoS One. 11(7):e0159360. doi: 10.1371/journal.pone.0159360.
Maree F, de Klerk-Lorist LM, Gubbins S, Zhang F, Seago J, Pérez-Martín E, Reid L, Scott K, van Schalkwyk L, Bengis R, Charleston B, Juleff N. (2016) Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence. J Virol. 90(10): 5132-40. doi: 10.1128/JVI.00166-16
Maree FF, Nsamba P, Mutowembwa P, Rotherham L, Esterhuysen J, Scott K. (2015) Intra-serotype SAT2 chimeric foot and mouth disease vaccine protects cattle against FMDV challenge. Vaccine. 33: 2909-2916. doi: 10.1016/j.vaccine.2015.04.058.
Kotecha A, Seago J, Scott K, Burman A, Loureiro S, Ren J, Porta C, Ginn HM, Jackson T, Perez-Martin E, Siebert CA, Paul G, Huiskonen JT, Jones IM, Esnouf RM, Fry EE, Maree FF, Charleston B, Stuart DI. (2015) Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design. Nature Structural & Molecular Biology. 22(10): 788-798. doi:10.1038/nsmb.3096.
Opperman PA, Rotherham LS, Esterhuysen J, Charleston B, Juleff N, Capozzo AV, Theron J, Maree FF (2014) Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses. J Virol. 88(15): 8307-18 doi: 10.1128/JVI.00470-14.
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