The Effect of Repeat Inoculation of Field-Grazing Crossbred Calves with TLR 7/8 Agonist on the Duration of Protection against Diseases
Date
2019-07
Authors
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Publisher
University Of Ghana
Abstract
Effective control of tick-borne diseases in endemic regions requires control of a complex of pathogens rather than a single pathogen-disease entity. A separate vaccine targeting each pathogen is not feasible for a variety of reasons. Therefore, the most effective means of control is to use one intervention to target multiple pathogens. Presently, we have demonstrated that stimulation of innate immunity using a Toll-Like receptor 7/8 agonist (TLR7/8) protects against multiple pathogen strains including anaplasmosis and ECF in the crossbred calves.
These results, although represented compelling evidence of agonist-induced innate immune protection, the duration of immunity conferred by the agonist is unknown. In most disease endemic areas, challenge will occur within 6 months, and as shown in Ghana, often much sooner. Whether the current formulation and single dose provides innate immune stimulation over this window is a critical question that will require data to resolve. The current study tested the effect of the agonist on disease and disease-associated costs. The cost savings from reduction in treatment costs and avoided death loss can be used to establish a product cost profile. There were three groups of 25 calves. Group 1 was administered with a single dose (1ml) of TLR7/8 emulsion at Day 0, to stimulate the innate immunity prior to exposure to natural disease challenge by vector ticks on the field; Group 2 was identically administered with the TLR7/8 emulsion at Day 0, and repeated at day 28; Group 3 was designated as an untreated control (calves were not injected with TLR 7/8 emulsion). All calves were allowed to comingle and graze on the field. Clinical signs and the need for treatment were assessed daily by the resident veterinary personnel. Specifically, 5 distinct pathogen species were detected in the herd of crossbred calves examined. Anaplasma marginale represented the most prevalent pathogen species accounting for >70% of tick-borne infections among crossbred calves examined. Other infectious diseases detected included Dermatophilosis, Contagious Bovine Pleuropneumonia (CBPP) and Foot and Mouth Disease (FMD). All calves including those stimulated by injection with the agonist were infected with A. marginale within 7 days of exposure to field challenge. Calves from all groups were infected with at least one pathogen. There was no statistically significant difference in the mean numbers of pathogen species circulating in calves from various groups. Notably, all 25 (100%) animals from the group that was not injected with the TL7/8 emulsion required therapeutic treatments against at least one disease. In contrast, the need for treatments were 48% and 36% respectively among calves injected with 1ml and 2ml of the agonist. Although, the difference in the need for treatment between the stimulated groups was not significantly different (p =0.254) the survival analysis has revealed that calves stimulated twice had the highest probability (88%) of surviving as compared to those either stimulated once or were unstimulated (p <0.001). Importantly, of the twenty-five unstimulated calves, 15/25 (60%) died of clinical diseases including Anaplasmosis as compared with 14% deaths from the group that received TLR7/8 agonist stimulation. The Odds Ratio for survival is 13.6 (95% confidence interval of 1.2-152.2). While the confidence interval is wide, it does not overlap with 1, the null value, indicating the protection in the group receiving the TLR agonist has a high likelihood of representing a reproducible effect. There were significant differences in IgG2 production with respect to number of stimulations (p<0.000). Calves stimulated twice demonstrated a significantly higher percent inhibition of 77.07 as compared to either the cohorts that were stimulated once (68.56) or unstimulated (29.17). Generally, disease-related death of calves within the groups represented the major source of cost to the farmer. This was most significant among the unstimulated group (GHC 18000). The benefit cost ratio revealed that, the group stimulated twice (6.12) was the most cost effective as compared to groups stimulated once (4.15) and unstimulated (0.45). In summary, this study has identified that the TLR7/8 water-in-oil emulsion provides sufficient innate immune protection to mitigate severe disease upon natural exposure to multiple vector-borne pathogens during the first six to12 months of life. While a single inoculation that provides a long-lasting depot for sustained induction of innate immunity over the six to 12 month vulnerable period would be optimal, a minimally acceptable regimen would be monthly inoculations, feasible in small-holder farms where animals are housed locally and given that the final emulsion cost is estimated between US$0.05-0.20. Together these results provided the rationale for recommending multiple innate immune stimulations of young crossbred calves as the most cost effective approach to protecting field-grazing crossbred cattle against diseases in Ghana.
Description
MPhil. Animal Science
Keywords
Calves, TLR 7/8 Agonist