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

Abstract

The genetic diversity of the three Southern African Territories (SAT) types of foot-and-mouth disease virus (FMDV) reflects high antigenic variation, and indications are that vaccines targeting each SATspecific topotype may be needed. This has serious implications for control of FMD using vaccines as well as the choice of strains to include in regional antigen banks. Here, we investigated an intra-serotype chimeric virus, vSAT2 ZIM14 -SAT2, which was engineered by replacing the surface-exposed capsid-coding region (1B-1D/2A) of a SAT2 genome-length clone, pSAT2, with that of the field isolate, SAT2/ZIM/14/90. The chimeric FMDV produced by this technique was viable, grew to high titres and stably maintained the 1B-1D/2A sequence upon passage. Chemically inactivated, oil adjuvanted vaccines of both the chimeric and parental immunogens were used to vaccinate cattle. The serological response to vaccination showed the production of strong neutralizing antibody titres that correlated with protection against homologous FMDV challenge. We also predicted a good likelihood that cattle vaccinated with an intra-serotype chimeric vaccine would be protected against challenge with viruses that caused recent outbreaks in southern Africa. These results provide support that chimeric vaccines containing the external capsid of field isolates induce protective immune responses in FMD host species similar to the parental vaccine.

Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine

“…In the design of FMD vaccines, a powerful tool, reverse genetics technology permits us to improve not only growth and antigen yield but also antigen stability [7,26]. It is also reported previously that reverse genetics technology could be used to construct a capsid substituted FMDV vaccine strain [27,28], which was again proved in this study.…”

Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle

“…BHK-21 cell-culture infected fluids from vSAT2-wt, vSAT2-93Y and vSAT2-93H were harvested, inactivated and purified as described before [23]. The inactivated 146S fractions were quantified as described previously [38] and used for vaccine formulation.…”

“…The inactivated 146S fractions were quantified as described previously [38] and used for vaccine formulation. Three separate vaccines (vSAT2-wt, vSAT2-93Y and vSAT2-93H) of 6-8 mg each were formulated as double oil emulsions with Montanide ISA 206B (Seppic) as described [23].…”

“…Oropharyngeal (OP) fluid, tonsil swabs (TS) and blood were collected on 0, 2, 4, 7 and 10, 12, 14 days post-challenge (dpc). The animals were examined daily for fever (mild = 39.5-40°C, severe !40°C) and clinical signs (small lesion/healing vesicle = 1, moderate vesicles = 2; severe lesions = 3) and sedated as described [23].…”

“…Recent the manipulation of the biological properties of field or laboratory strains [17][18][19] and structural analyses of the capsid have allowed for the design of thermostable mutations [20,21] integrated into reverse genetic approaches [22,23]. Several studies have shown that chimeric vaccines successfully induce protective immune responses and protect FMD host species against live virus challenge [23][24][25]. Additionally, the SAT capsid can be engineered to encode antigens required for vaccines in specific geographic localities [25] and for improved cell adaptation properties [26,27].…”