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

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-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of 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. As these qualities are necessary for vaccine manufacturing, high titres of stable chimeric 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 with 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 that they induce protective immune responses in FMD host species.

Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge

“…We did not measured the antibody avidity or the role of cell-mediated response in this experiment and it is therefore not unreasonable to expect that the single immunization of cattle did not allow sufficient development of high avidity antibodies through affinity maturation or the development of optimal isotypes in some individual animals. The individual variation to vaccines is well documented and has been observed for chimeric vaccines as well [26,33].…”

“…The proposed strategy entails the development of chimeric FMDV by substituting antigenic-coding regions such as the external capsid proteins (1B-1D/2A) in an infectious genomelength cDNA clone of a suitable strain [34]. The production of such recombinant viruses has been achieved for the A and SAT2 serotypes [26,30,33]. In the present study, the efficacy of an intra-serotype SAT2 chimeric vaccine was assessed.…”

“…Chimeric, genome-length clones could form the basis for the rational engineering of viruses with improved structural features as vaccine seed viruses. Viruses can be engi-neered with structurally stabilising mutations to be less reliant on a faultless cold chain [25,26,51], with BHK-21 cell culture adap-tation and increased antigen yield [31] or defective FMDV can be generated with deletions in various parts of the genome [52][53][54]. Furthermore, viruses can be engineered with modifications incorporated into the genome to support serological differentiation of infected from vaccinated animals [33] for surveillance of FMD in sub-Saharan Africa.…”

“…We have structurally-engineered recombinant SAT viruses, containing desirable antigenic determinants and cell adaptation phenotypes [28,31,32] providing the proof-of-concept to rationally design viruses with the desired biological properties of a good vaccine strain. Several studies have shown that inter-serotype chimeric vaccines successfully induce protective immune responses and protect FMD host species against live virus challenge [26,30,33]. Additionally, the SAT capsid can be engineered to be thermo-stable, produce high 146S antigen mass following chemical inactivation and provide appropriate immunological specificity whilst encoding the antigens required for vaccines in specific geographic localities.…”

“…One approach is to structurally design vaccines for specific geo-graphic regions [25,26]. The fact that the viral RNA can be made infectious in the absence of other components of the virion (reverse genetics) opened the theoretical possibility of genetically engineer-ing new viruses from in vitro-generated RNA molecules [24,27].…”