Low-dose BCG vaccination protects free-ranging cattle against naturally-acquired bovine tuberculosis.

Vaccination of cattle with Mycobacterium bovis BCG has been shown to protect against infection with virulent strains of M. bovis, and against resultant bovine tuberculosis (TB). Here we report on a large-scale trial in New Zealand where free-ranging cattle were vaccinated with 3 x 105 BCG via injection, a lower dose than any previously trialed in cattle against exposure to a natural force of M. bovis infection. In a multi-year enrolment study involving >800 animals, three cohorts of 1-2 year old cattle were randomised to receive vaccine or to serve as non-vaccinated controls. Cattle were slaughtered and subject to standard abattoir post mortem examination for M. bovis culture-positive TB lesions after up to 3.7 years of in-field exposure; additionally, lymph node samples from approximately half of the cattle were examined further to identify infection in the absence of lesions. Overall TB prevalence, as identified by gross lesions detected at slaughter, was low among farmed cattle at the study site (<4% annually). There were two lesioned cases among 520 vaccinated trial cattle (0.38%) compared to eight among 297 non-vaccinated trial cattle (2.69%). Trial vaccine efficacy was 85.7% against abattoir-detectable TB (statistically significant protection), and 86.7% when adjusted for duration of exposure. BCG vaccination did not significantly affect the response rates of cattle to ante mortem skin- or blood-tests in diagnostic tests conducted >7 months post-vaccination. Use of a reduced, yet effective, dose of BCG would increase the cost effectiveness of using this vaccine in a bovine TB control programme.

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

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.

Assessing Movements of Brushtail Possums (Trichosurus vulpecula) in Relation to Depopulated Buffer Zones for the Management of Wildlife Tuberculosis in New Zealand.

In New Zealand, managing the threat of bovine tuberculosis (TB) to livestock includes population reduction of potentially infectious wildlife, primarily the brushtail possum (Trichosurus vulpecula). Population control is often targeted on forested buffer zones adjacent to farmland, in order to limit movements of possums across the buffer and reduce the risk of disease transmission to livestock. To assess the effectiveness of buffers in protecting livestock we analysed GPS telemetry data from possums located in untreated forest adjacent to buffers, and used these data to characterise patterns of movement that could lead to possums reaching farmland during the season when most dispersal occurs. Analyses of movement data showed that the direction of dispersal by sub-adult and adult possums and the extent of long exploratory movements were not biased toward forest buffers, even though these provided vacant habitat as suitable for possums as untreated forest. Instead, dispersal and exploratory movements were uncommon even for sub-adult possums and such events typically lasted <10 days. Dispersing possums settled predominantly in river valleys. A simulation model was developed for the 3-6-month dispersal season; it demonstrated a probability of <0.001 that an infected possum, originating from a low-density population with low disease prevalence in untreated forest, would move across 3 km of recently controlled forest buffer to reach farmland. Our results indicate short-term reduction in the risk of TB transmission from possums to livestock in New Zealand by the use of depopulated buffer zones, while acknowledging that the threat of disease spread from untreated forest is likely to increase over time as possum population density and, potentially, TB prevalence among those possums, increase in the buffer zone.

Quantifying short-term foraging movements in a marsupial pest to improve targeted lethal control and disease surveillance.

In New Zealand, the introduced marsupial brushtail possum (Trichosurus vulpecula) is a pest species subject to control measures, primarily to limit its ability to transmit bovine tuberculosis (TB) to livestock and for conservation protection. To better define parameters for targeted possum control and TB surveillance, we here applied a novel approach to analyzing GPS data obtained from 44 possums fitted with radio-tracking collars, producing estimates of the animals' short-term nocturnal foraging patterns based on 1-, 3- or 5-nights' contiguous data. Studies were conducted within two semi-arid montane regions of New Zealand's South Island High Country: these regions support low-density possum populations (<2 possums/ha) in which the animals' home ranges are on average larger than in high-density populations in forested habitat. Possum foraging range width (FRW) estimates increased with increasing monitoring periods, from 150-200 m based on a single night's movement data to 300-400 m based on 5 nights' data. The largest average FRW estimates were recorded in winter and spring, and the smallest in summer. The results suggest that traps or poison-bait stations (for lethal control) or monitoring devices (for TB surveillance), set for > 3 consecutive nights at 150 m interval spacings, would likely place >95% of the possums in this type of habitat at risk of encountering these devices, year-round. Modelling control efficacy against operational expenditure, based on these estimations, identified the relative cost-effectiveness of various strategies that could be applied to a typical aerial poisoning operation, to reduce the ongoing TB vectorial risk that possums pose in the High Country regions. These habitat-specific findings are likely to be more relevant than the conventional pest control and monitoring methodologies developed for possums in their more typical forested habitat.

Mortality rate and gross pathology due to tuberculosis in wild brushtail possums (Trichosurus vulpecula) following low dose subcutaneous injection of Mycobacterium bovis.

Gross pathology due to tuberculosis can be established experimentally in brushtail possums (Trichosurus vulpecula) within 7 weeks of injection of virulent Mycobacterium bovis into subcutaneous connective tissues of the peripheral limbs. This pathology involves lymphadenomegaly and development of gross lesions in peripheral lymph nodes, with subsequent gross lesions in the lungs and reticuloendothelial organs. Using this artificial infection model, we here assessed the mortality rate for possums in the wild, to provide new information on the likely survival period for New Zealand's major wildlife host. Possums were trapped and inoculated with <50 CFU of M. bovis, then fitted with mortality signal emitting radio tracking collars, released and re-tracked for 6 months. Possum survival probability was 89% up to 12 weeks post-injection (p.i.), but cumulative mortality was rapid from then on. The median survival period, based on study of 38 possums, was 18 weeks p.i.; this corresponds with a predicted time interval of 11 weeks between first presentation of TB as palpable lymphadenomegaly and death for an average possum, shorter than period values currently used in possum TB epidemiological modelling. We also examined gross pathology in 11 possums by post mortem necropsy, and confirmed lymphadenomegaly and tuberculous lesions at 7 and 12 weeks p.i. Extra-peripheral gross lesions were more frequent among possums at 12 weeks p.i. than at 7 weeks, while the occurrence of lung lesions (the most likely cause of disease-induced mortality) was apparent in animals at 12 weeks but not at 7 weeks p.i. Our results suggest that the time course of TB from development of gross lesions to mortality may be shorter than previously estimated from field studies of naturally tuberculous possums.

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

BACKGROUND: Vaccination of wildlife against bovine tuberculosis (TB) is being considered by several countries to reduce the transmission of Mycobacterium bovis infection to livestock. In New Zealand, where introduced brushtail possums (Trichosurus vulpecula) are the major wildlife hosts, we have previously shown that repeat applications of a lipid-encapsulated oral bacille Calmette-Guerin (BCG) vaccine reduce the incidence of naturally acquired TB in wild possums. Here we extend this conceptual demonstration to an operational level, assessing long-term protection against TB conferred to free-living possums by a single oral immunisation. METHODS: Possums in a non-TB area were randomly allocated to receive lipid-formulated BCG vaccine or remained unvaccinated. After initial trials to assess vaccine immunogenicity and establishment of protection within the first year post-vaccination, 13 individuals of each treatment group were relocated to a biosecurity facility and challenged (at 28 months post-vaccination) by subcutaneous injection of virulent M. bovis. RESULTS: Vaccine immunogenicity and short-term protection were confirmed at 2 months and 12 months post-vaccination, respectively. In the long-term assessment, vaccinated possums had significantly reduced bacterial counts in peripheral lymph nodes compared to controls, with 0.6-2.3 log(10)-fold reductions in M. bovis burdens. DISCUSSION: The magnitude of protective response by possums to experimental challenge at 28 months post-vaccination is known to equate to a high degree of protection against natural infection in this species. With techniques for oral bait delivery well advanced, the longevity of protection demonstrated here shows that an operable wildlife vaccine against TB is feasible.

Bait aggregation to reduce cost and toxin use in aerial 1080 baiting of small mammal pests in New Zealand.

BACKGROUND: The metabolic toxin sodium fluoroacetate ('compound 1080') is widely used for controlling introduced mammalian pests in New Zealand. For large-scale operations, 1080 is distributed aerially in bait to kill brushtail possums (Trichosurus vulpecula Kerr) and ship rats (Rattus rattus L.). While usually successful in reducing pest populations by > 80%, widespread distribution of toxic bait is relatively expensive and raises concerns from some members of the public. Here, trials with spatial aggregation of baits in forested habitats were conducted to determine whether this can reduce toxin usage while maintaining operational efficacy. RESULTS: When 1080 baits were aggregated into clusters (by hand sowing) or into strips (by precision aerial deployment), indices of possum relative abundance were reduced by 92-100%, compared with 73-100% reductions using conventional aerial broadcasting, while all methods reduced relative abundance indices of rats by 88% or greater. Radio tracking indicated a kill rate of > 90% against possums, regardless of bait distribution method. CONCLUSIONS: Simply by modifying bait distribution patterns, spatial aggregation can be used to maintain the high encounter rate of pests with 1080 bait that is necessary for operational efficacy, while reducing current toxin usage by up to 80%. Aggregated bait delivery could have relevance for other mammalian pest control scenarios internationally.

Vaccinia virus as a vaccine delivery system for marsupial wildlife.

Vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. They have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. In some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial. Here, we report a study of the potential for vaccination using vaccinia virus in the Australian brushtail possum Trichosurus vulpecula, an introduced pest species in New Zealand. Parent-strain vaccinia virus (Lister) infected 8/8 possums following delivery of virus to the oral cavity and outer nares surfaces (oronasal immunisation), and persisted in the mucosal epithelium around the palatine tonsils for up to 2 weeks post-exposure. A recombinant vaccinia virus construct (VV399, which expresses the Eg95 antigen of the hydatid disease parasite Echinococcus granulosus) was shown to infect 10/15 possums after a single-dose oronasal delivery and to also persist. Both parent vaccinia virus and the VV399 construct virus induced peripheral blood lymphocyte reactivity against viral antigens in possums, first apparent at 4 weeks post-exposure and still detectable at 4 months post-exposure. Serum antibody reactivity to Eg95 was recorded in 7/8 possums which received a single dose of the VV399 construct and 7/7 animals which received triple-dose delivery, with titre end-points in the latter case exceeding 1/4000 dilution. This study demonstrates that vaccinia virus will readily infect possums via a delivery means used to deploy wildlife vaccines, and in doing is capable of generating immune reactivity against viral and heterologous antigens. This highlights the future potential of recombinant vaccinia virus as a vaccine delivery system in marsupial wildlife.

Effect of bovine colostrum supplementation on respiratory tract mucosal defenses in swimmers.

PURPOSE: This study investigated the effect of bovine colostrum (BC) on mucosal defense in the respiratory tracts of athletes and a nonexercising control group. METHODS: An athlete cohort (ATH) of 25 (12 male, 13 female) elite swimmers (age 14-23 yr) and a control cohort (CON) of 28 (9M, 19F) students (age 18-27 yr) were randomly allocated in a double-blind manner to receive either 25 g BC (low-protein colostrum powder) or isocaloric placebo (PL) per day for 10 wk. Postprandial saliva samples were analyzed for immunoglobulins (A, G, and M) and osmolality at baseline, after 4 and 10 wk, and 2 wk postsupplementation. Blood samples were analyzed for immunoglobulins and C-reactive protein at baseline, after 5 and 10 wk, and 2 wk postsupplementation. Dietary intake was assessed by self-recorded dietary records. Upper respiratory tract symptoms (URS) and exercise were also self-recorded daily. RESULTS: There was no significant time-related effect of the BC supplement on either saliva or plasma immunoglobulin levels for either cohort. After 4 wk supplementation fewer ATH/BC (25%) than ATH/PL participants (61%) reported URS incidents (p = .062). No significant difference occurred in URS reports in the control group. CONCLUSION: There was no measurable effect on immunoglobulin levels of consuming BC, which is in contrast to effects that have been reported previously in marathon runners, indicating that the effect of BC supplementation is not universal in all groups of athletes. Fewer athletes reported URS (although cause unknown) when consuming BC, which may be advantageous for training.

Age-related differences in integrin expression in peripheral blood lymphocytes.

Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (alpha4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence.

Antimicrobial and immunomodulatory activities of an ovine proline/arginine-rich cathelicidin.

In in vitro co-culture experiments, the ovine-derived cathelicidin OaBac5mini showed antimicrobial activity against Escherichia coli cells and modulated production of a cytokine by a mammalian inflammatory cell type (macrophage). Using atomic force microscopy, the morphology of peptide-treated E. coli bacteria showed no cell lysis, indicating an intracellular mode of action of the peptide leading to bacterial cell inhibition. At a concentration of 50microg/mL OaBac5mini, the peptide suppressed production of the inflammatory cytokine interleukin-12 by murine J774A cells that had been stimulated with Staphylococcus aureus strain Cowan; levels of other cytokines were unaffected. Thus, certain cationic peptides can enter and disrupt invading Gram-negative pathogens and may be able to modulate inflammatory responses induced by Gram-positive bacterial products.

Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either.

An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

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 oral-delivery 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.

Immunogenicity of orally-delivered lipid-formulated BCG vaccines and protection against Mycobacterium tuberculosis infection.

Lipid formulations containing BCG strains Danish 1331 or Moreau (Rio de Janeiro) were trialled as oral vaccines in rodent models. In mice, oral-delivery of either strain resulted in BCG colonisation of the alimentary tract lymphatics and induction of gamma-interferon responses. In guinea pigs, both strains provided pulmonary protection against Mycobacterium tuberculosis aerosol challenge, as shown by significantly reduced bacterial loads and lung:body weight ratios. Lipid-formulated BCG provided superior protection against M. tuberculosis over unformulated orally-delivered BCG (Moreau), and equivalent protection to sub-cutaneous BCG (Danish) immunisation. Oral-delivery of lipid-formulated BCG may offer a practical alternative to parenteral-route BCG vaccination.

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.

Oral vaccination of guinea pigs with a Mycobacterium bovis bacillus Calmette-Guerin vaccine in a lipid matrix protects against aerosol infection with virulent M. bovis.

Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with Mycobacterium bovis is a cause of considerable economic loss to farmers and the government. The Eurasian badger (Meles meles) represents a wildlife source of recurrent M. bovis infections of cattle in the United Kingdom, and its vaccination against TB with M. bovis bacillus Calmette-Guérin (BCG) is an attractive disease control option. Delivery of BCG in oral bait holds the best prospect for vaccinating badgers over a wide geographical area. Using a guinea pig pulmonary challenge model, we evaluated the protective efficacy of candidate badger oral vaccines, based on broth-grown or ball-milled BCG, delivered either as aqueous suspensions or formulated in two lipids with differing fatty acid profiles (one being animal derived and the other being vegetable derived). Protection was determined in terms of increasing body weight after aerosol challenge with virulent M. bovis, reduced dissemination of M. bovis to the spleen, and, in the case of one oral formulation, restricted growth of M. bovis in the lungs. Only oral BCG formulated in lipid gave significant protection. These data point to the potential of the BCG-lipid formulation for further development as a tool for controlling tuberculosis in badgers.

Murine cytokine responses following multiple oral immunizations using lipid-formulated mycobacterial antigens.

Oral vaccination of mice with live Mycobacterium bovis BCG in lipid-formulation induces a gamma-interferon response that can be measured systemically, and confers protection against aerosolized mycobacterial challenge. Here, we have investigated cytokine responses following the vaccination, drawing comparisons between mice that received single or multiple oral immunizations and between mice receiving formulations containing live BCG or non-replicating mycobacterial antigens. Single oral immunization with lipid-formulated live BCG invoked secreted and cellular IFN-gamma responses in mice 8 weeks post-vaccination, the magnitudes of which were significantly elevated in mice receiving multiple immunizations over the 8-week period. Single oral immunization with live BCG also invoked an interleukin-2 response (but not TNF-alpha or IL-4), although the magnitude was not elevated by multiple immunizations. Multiple immunizations with lipid-formulated soluble or particulate non-replicating mycobacterial antigens failed to invoke cytokine responses, except for a low-level IFN-gamma response in mice multiple immunized with lipid-formulated heat-killed BCG. These results are discussed in contrast to the known patterns of cytokine induction following parenteral-route immunization with live or non-replicating mycobacterial antigens and with practical reference to the development of oral-delivery vaccines against tuberculosis.

Oral vaccination against bovine tuberculosis with Mycobacterium bovis BCG.

The use of a bacillus Calmette-Guerin (BCG)-based vaccine could represent a viable strategy for controlling bovine tuberculosis (TB), principally in those cases where a wildlife disease vector exists. This article focuses on recent progress in animal TB vaccinology, outlining that oral-route vaccination represents the most feasible means of distributing a vaccine to control disease in wildlife. Drawing on historical successes of previous wildlife vaccination programs, the article suggests how, and in what form, an oral-delivery BCG-based vaccine might become operational, considering the wide diversity of TB reservoir species and the inherent problems associated with field delivery of a live-attenuated microbial vaccine.

The effect of bovine colostrum supplementation on salivary IgA in distance runners.

Secretory IgA in saliva (s-IgA) is a potential mucosal immune correlate of upper respiratory tract infection (URTI) status. Nutritional supplements may improve mucosal immunity, and could be beneficial to athletes who are at increased risk of URTI. In this study, 35 distance runners (15 female, 20 male, age 35 to 58 y) consumed a supplement of either bovine colostrum or placebo for 12 wk. Saliva samples were taken prior to training at baseline, monthly during supplementation, and 2 wk post supplementation. Median levels of s-IgA increased by 79% in the colostrum group after 12 wk intervention, and the time-dependent change from baseline value was significant (P = 0.0291). This significance was still apparent after adjusting for training volume and self-reporting of upper respiratory symptoms. This study has demonstrated increased s-IgA levels among a cohort of athletes following colostrum supplementation. While this result is statistically significant, its physiological interpretation must be viewed with caution due to the small numbers in this study and the large variability in s-IgA levels.