Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage

Abstract

In 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East were discovered to be caused by a viral lineage (A/ASIA/G-VII), which has recently emerged from the Indian sub-continent. In vitro vaccine matching data generated by the World Reference Laboratory (WRLFMD) indicated that A/ASIA/G-VII field viruses were poorly matched with vaccines (A-SAU-95, A22 IRQ and A-IRN-05) that are already used in the region. In order to assess the likely performance of one of these commercially available FMD vaccines, sixteen cattle were vaccinated with a polyvalent vaccine which contained two serotype A components (A-SAU-95 and A-IRN-05) with a homologous potency of at least 6PD₅₀, and two cattle were left unvaccinated as controls. Twenty-one days later, all 18 cattle were challenged by tongue inoculation with an FMDV field isolate A/IRN/22/2015 from the A/ASIA/G-VII lineage, in line with the European Pharmacopeia PPG test conditions. The two control animals developed generalised FMD, and 7/16 vaccinated animals developed at least one foot lesion, thus only 56.3% were defined as protected. For the vaccine components, there was a significant increase in the probability of protection with increasing serological titres for A-SAU-95 (p = 0.03), but not for A-IRN-05 (p = 0.42). Analysis of FMDV in blood and nasal swabs suggested that vaccination reduced shedding and potential onward spread of FMD virus even if the animal developed foot lesions. In summary, the results from this study suggest that whilst this vaccine would not be appropriate for use in an emergency situation (in previously FMD-free countries), it may be partially effective in the field in endemic countries where repeat prophylactic vaccination is practiced. For emergency reactive vaccination, the findings from this study support the idea that a new vaccine strain should be developed that is tailored to the A/ASIA/G-VII lineage.

Keywords: A/ASIA/G-VII; Challenge; Foot-and-mouth disease virus; Podal generalisation test (PPG); Vaccine.

Fig. 1

Mean daily rectal temperatures for all cattle before and after challenge with A/IRN/22/2015. Mean daily rectal temperatures for all cattle before (days post vaccination: DPV) and after challenge (days post challenge: DPC) with A/IRN/22/2015. Unvaccinated (⋅⋅⋅⋅⋅), vaccinated-lesions (− − −) and, vaccinated-no lesions (—) are all shown as separate line designs. Error bars represent the standard error. Horizontal dashed line is drawn at 39.5 °C; temperatures above which were classed as pyrexia.

Fig. 2

Serological responses on day 21 (day of challenge) of cattle given a full dose of the multivalent vaccine. Serological responses are displayed by plotting the reciprocal neutralising titre of each animal’s serum on the day of challenge when tested against the challenge virus (A) and each of the serotype A components of the vaccine (B and C). Animals are grouped into whether they developed foot lesions or no foot lesions. The two animals with foot lesions having a titre of <8 (denoted as*) are the two unvaccinated controls.

Fig. 3

Graphs showing viral RNA levels over time in cattle challenged with A/IRN/22/2015. (A) Mean daily RNA concentrations in the serum for each time point for each of the 3 groups of animals (unvaccinated (⋅⋅⋅⋅⋅), vaccinated-lesions (− − − −) and, vaccinated-no lesions (—)). (B) Area under the curve (AUC) plotted for each animal, with animals grouped into the same 3 groups.

Fig. 4

Graph showing quantities of live FMDV on nasal swabs taken daily from challenged animals. Total nasal shedding of FMDV over time. This is represented by calculating the area under the curve (AUC) for each animals daily FMDV shedding, and grouped into Vaccinated-no lesions, Vaccinated-lesions, and Unvaccinated.