Lipid-Formulated BCG as an Oral-Bait Vaccine for Tuberculosis: Vaccine Stability, Efficacy, and Palatability to Brushtail Possums (Trichosurus Vulpecula) in New Zealand

Abstract

ABSTRACT:Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oraldelivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km 2 . Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10 8 BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

Sustained protection against tuberculosis conferred to a wildlife host by single dose oral vaccination

“…In the case of the lipid-formulated BCG vaccine, the first two criteria have clearly been met. First, the vaccine matrix has been demonstrated as edible and can be flavoured to act as a bait attractant [38], while techniques for the delivery of baits to possums are well advanced with aerial dissemination able to reach over 90% of the individuals in a population [39]. Second, oral-delivery of the lipid-formulated BCG vaccine reduces the incidence of naturally acquired TB in a wild possum population by 95-96% [9], with modelling studies indicating that the maintenance of only 40-52% of a possum population in an immune state is sufficient for TB eradication [40,41].…”

Vaccination against tuberculosis in badgers and cattle: an overview of the challenges, developments and current research priorities in Great Britain

“…Experimental studies in possums have suggested that in order to generate immunity it is necessary for oral BCG to retain viability up until the point of delivery to the intestine (Buddle and others 2006). This has been facilitated through the formulation of BCG in a lipid matrix that provides a stable storage and delivery vehicle (that protects the live attenuated bacillus during passage through the stomach) (Cross and others 2009). Recent success using heat-inactivated M bovis to experimentally vaccinate wild boar orally has increased the number of candidate oral vaccines for TB (Garrido and others 2011, Beltran-Beck and others 2014).…”

Evaluation of attractant flavours for use in oral vaccine baits for badgers (Meles meles)

“…Attractiveness and palatability can be influenced by the presentation, construction and composition of the baits. Recent developments in an oral vaccine for tuberculosis (Aldwell et al 2003a, b;Cross et al 2009;Tompkins et al 2009) have resulted in the production of solid lipid baits that can be used to encapsulate live BCG bacilli. When delivered by the oral route, lipid-formulated BCG has been shown to induce protection in brushtail possums (Tompkins et al 2009) and badgers (Corner et al 2010).…”