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Title: Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

item BLIGNAUT, BELINDA - Onderstepoort Veterinary Institute
item VISSER, NICO - Intervet - Netherlands
item THERON, JACQUES - University Of Pretoria
item Rieder, Aida - Elizabeth
item MAREE, FRANCOIS - Onderstepoort Veterinary Institute

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2010
Publication Date: 4/1/2011
Citation: Blignaut, B., Visser, N., Theron, J., Rieder, A.E., Maree, F.F. 2011. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs. Journal of General Virology. 92(4):849-859.

Interpretive Summary: Foot-and-mouth disease (FMD) is a devastating disease of cloven hooved animals caused by any of seven serotypes (A, O, C, Asia, SAT1, SAT2 and SAT3) and multiple subtypes of FMD virus. Current vaccines do not induce protective immune responses across serotypes or, in many cases, subtypes. In this report, the feasibility of an FMDV vaccine containing parts of the SAT1/SAT2 serotypes (chimeric vaccine) was assessed by determining the immunogenicity and protective ability following immunization of pigs. We demonstrated that the chimeric vaccine exhibited similar tissue culture growth characteristics, virion stability and antigenic profiles to the SAT1 parental virus. Pigs vaccinated with the chimeric vaccine showed good immune responses and the majority of the animals were protected against homologous (SAT1) FMDV challenge. Furthermore, these results suggest that custom-engineered chimeric FMD vaccines can be produced and applied in a fashion similar to the current inactivated vaccines.

Technical Abstract: Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-coding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of the SAT1 virus KNP/196/91. The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and antigenic profiles to the KNP/196/91 parental virus, thus indicating that the functions provided by the capsid can be readily exchanged between serotypes. With these qualities necessary for vaccine manufacturing, high titres of stable chimera virus were obtained. Chemically inactivated vaccines, formulated as double-oil-in-water emulsions, were produced from intact 146S virion particles of both the chimeric and parental viruses. Inoculation of guinea pigs with the respective vaccines induced similar antibody responses. In order to show compliance to commercial vaccine requirements the vaccines were evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralizing antibodies and showed protection against homologous FMDV challenge, albeit not to the same extent as for the vaccine prepared from the parental virus. These results provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and induces protective immune responses in FMD host species.