Field Trial of an Aerially-Distributed Tuberculosis Vaccine in a Low-Density Wildlife Population of Brushtail Possums (Trichosurus vulpecula)

Abstract

Oral-delivery Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine in a lipid matrix has been shown to confer protection against M. bovis infection and reduce the severity of tuberculosis (TB) when fed to brushtail possums (Trichosurus vulpecula), the major wildlife vector of bovine TB in New Zealand. Here we demonstrate the feasibility of aerial delivery of this live vaccine in bait form to an M. bovis-infected wild possum population, and subsequently assess vaccine uptake and field efficacy. Pre-trial studies indicated a resident possum population at very low density (<0.6 possums/ha) at the field site, with a 5.1% prevalence of macroscopic TB lesions. Pilot studies indicated that flavoured lipid matrix baits in weather-proof sachets could be successfully sown aerially via helicopter and were palatable to, and likely to be consumed by, a majority of wild possums under free-choice conditions. Subsequently, sachet-held lipid baits containing live BCG vaccine were sown at 3 baits/ha over a 1360 ha area, equating to >5 baits available per possum. Blood sampling conducted two months later provided some evidence of vaccine uptake. A necropsy survey conducted one year later identified a lower prevalence of culture-confirmed M. bovis infection and/or gross TB lesions among adult possums in vaccinated areas (1.1% prevalence; 95% CI, 0–3.3%, n = 92) than in unvaccinated areas (5.6%; 0.7–10.5%, n = 89); P = 0.098. Although not statistically different, the 81% efficacy in protecting possums against natural infection calculated from these data is within the range of previous estimates of vaccine efficacy in trials where BCG vaccine was delivered manually. We conclude that, with further straightforward refinement to improve free-choice uptake, aerial delivery of oral BCG vaccine is likely to be effective in controlling TB in wild possums. We briefly discuss contexts in which this could potentially become an important complementary tool in achieving national eradication of TB from New Zealand wildlife.

Development and Challenges in Animal Tuberculosis Vaccination

“…Complement component C3 was identified as naturally associated with TB vaccine protection in wild boar [36], red deer [17,98] and zebrafish (Danio rerio) [39,125]. Different studies in domestic animals and wildlife have also shown how BCG induced an innate trained immune response by aerosol, oral or parenteral route [18,75,121,126]. This was also observed in goats vaccinated intranasally and subcutaneously with SO 2 and MTBVAC, respectively [48,87].…”

“…Detailed lesion scoring (macroscopic and microscopic) is a common practice to determine the degree of vaccine-induced protection in laboratory trials [15,18,23,26,27,36,39,75,89]. Total lesion prevalence was used to determine vaccine efficacy in field trials in cattle and wildlife TB studies [8,14,38,53,[119][120][121]. The studies with BCG and HIMB (parenteral/oral) reduced the total disease burden, especially the thoracic lesions in goats, deer, wild boar and badgers experimentally challenged with M. bovis [17,18,36,48,89,91] or in field studies [14,38,65].…”

“…As well as in badgers, vaccination of possums has been proposed as a TB control measure. BCG (Pasteur or Danish) has been the vaccine of choice in almost all trials, and both strains have induced protection using different routes-conjunctival, intranasal aerosol, oral, intragastric, intraduodenal, subcutaneous-and doses [163,164], even in field conditions [121,165,166] (Table 6). Some products such as ranitidine have shown to reduce gastric acidity and improved the efficacy of intragastrically administered BCG [108].…”

Animal tuberculosis: impact of disease heterogeneity in transmission, diagnosis, and control

“…Cattle vaccination with attenuated M. bovis BCG can negatively interfere with the intradermal tuberculin test applied by routine for diagnosis, so it is forbidden in several countries, including the European Union (EU) member states. However, several experimental trials are currently being conducted in wildlife hosts, such as badger (Aznar et al, 2018; Gormley et al, 2017) and wild boar (Díez‐Delgado et al, 2018; Garrido et al, 2011) in Europe or brushtail possum (Nugent et al, 2016) in New Zealand. The specific characteristics of the vaccine ( M. bovis BCG or heat‐inactivated M. bovis ; with or without adjuvants); the administration method (oral, parenteral); the characteristics of oral baits; and, in field trials, the unknown immune condition of the host undergoing vaccination together with the number of times the same individual could be in contact with the vaccine all contribute to shaping the (variable) immune response (Aznar et al, 2018; Chambers et al, 2017; Díez‐Delgado et al, 2018; Gormley et al, 2017; Nugent et al, 2016).…”

In Vitro Evaluation of Eudragit Matrices for Oral Delivery of BCG Vaccine to Animals

“…More convincingly, intra-gastric administration of BCG to brush-tailed possums (the principal wildlife reservoir of TB in New Zealand) was less effective than vaccine administered by the same route in combination with a drug to reduce gastric acidity or when administered intra-duodenally [12,13]. Protection of BCG against degradation in the gut is also the basis of efforts to formulate BCG in a lipid matrix for oral delivery to wildlife [14][15][16].…”