Oral vaccination of brushtail possums with BCG: Investigation into factors that may influence vaccine efficacy and determination of duration of protection

Abstract

Factors considered potentially capable of interfering with vaccination, including feeding dead BCG to possums prior to feeding live BCG, feeding multiple doses of BCG at one time, and changing strains of BCG, were shown not to interfere with the acquisition of protective immune responses in possums. Protection against tuberculosis was undiminished up to 29 weeks after vaccination with BCG administered orally. It is concluded that vaccination of possums by feeding pellets containing BCG is a robust and efficient approach to enhance the resistance of these animals to tuberculosis.

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

“…Previous studies with lipid-based possum vaccines have indicated that it is possible to formulate up to 10 8 viable BCG bacteria per dose (Wedlock et al, 2005;Buddle et al, 2006), while laboratory-based studies have suggested that a minimal effective dose for the lipid-formulated vaccine is approximately 10 7 viable bacilli per dose (Cross et al, 2007b): hence, a theoretical drop in bacterial viability of 1 log 10 from the original (time 0) value was set as the determination point for vaccine stability. For bait preference studies, statistical significance was determined by rank test analysis of the order in which possums accepted each flavored bait.…”

“…Previous studies on captive possums have indicated that lipid-based oral BCG vaccines can induce cell-mediated immune responses and can limit the incidence and/or severity of Tb due to M. bovis infection (Aldwell et al, 2003a;Wedlock et al, 2005;Buddle et al, 2006; Lesions in the spleen or liver (two control animals had splenic lesions, one had liver lesions).…”

“…Concanavalin A (Con A, Sigma, St Louis, Missouri) was used as the T cell mitogen control (25 mg/ml final concentration). At 8 wk postvaccination, all possums were sedated and their respiratory tracts exposed to an estimated dose of 10-20 virulent M. bovis strain 83/6235 bacilli/animal, via an aerosol-generating apparatus as described (Aldwell et al, 2003a;Buddle et al, 2006). Postchallenge weight changes were monitored regularly, and possums were subsequently euthanized 8 wk postchallenge and subjected to detailed postmortem examination.…”

“…A key factor in the success of these programs has been the use of live, avirulent vaccine microorganisms, which retain immunogenicity via oral delivery; the corollary to this is that any baiting system designed to deliver a live, attenuated micro-organism in the field must also be nontoxic to the live vaccine and must not detrimentally affect its immunogenicity. The existing Tb vaccine (M. bovis, strain BCG) is similarly a live, attenuated micro-organism, and oral vaccination studies have shown that it is necessary for BCG to be delivered live in order to generate effector immunity (Aldwell et al, 2006;Cross et al, 2008).…”

“…Previous research has demonstrated that edible lipid matrices provide an effective delivery vehicle for live BCG bacilli (Aldwell et al, 2003b), as the basis of an oral vaccine against Tb in possums ( Aldwell et al, 2003a;Buddle et al, 2006;Collins et al, 2007). Edible lipids are thought to protect BCG during transit through the gastrointestinal tract, thus delivering live bacilli to intestinal sites of immune induction.…”