Cattle may provide a suitable model for testing ways of improving tuberculosis vaccine efficacy in human infants. A vaccination and challenge study was undertaken in calves to determine the optimal time to vaccinate neonatal animals with Mycobacterium bovis bacillus Calmette-Guérin (BCG) for protection against tuberculosis and to determine whether revaccination with BCG was beneficial. Calves (10 per group) were vaccinated with BCG within 8 h of birth or at 6 weeks of age, when immune responses to antigens of environmental mycobacteria were detectable, or vaccinated at birth and revaccinated at 6 weeks. A control group was not vaccinated. BCG vaccination at birth induced strong antigen-specific gamma interferon (IFN-␥) and interleukin-2 (IL-2) responses and antigen-specific activation in CD4؉ , CD8 ؉ , and WC1 ؉ ␥␦ T-cell subsets from blood. The proportions of animals per group with macroscopic tuberculous lesions after challenge were 0/10 for BCG at birth, 1/9 for BCG at 6 weeks, 4/10 for the revaccinated group, and 10/10 for the nonvaccinated group. There was no significant difference in the levels of protection between groups vaccinated at birth or at 6 weeks, while animals vaccinated both at birth and at 6 weeks had significantly less protection than those vaccinated only at birth. The revaccinated calves that subsequently developed tuberculous lesions had significantly stronger IFN-␥ and IL-2 responses to bovine purified protein derivative after the BCG booster than those in the same group that did not develop lesions. The results indicated that BCG vaccination at birth induced a high level of immunity and that the sensitization of very young animals to antigens of environmental mycobacteria by 6 weeks of age did not affect the effectiveness of BCG. However, BCG revaccination of these young animals was contraindicated.

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Ruminant-derived methane (CH 4 ), a potent greenhouse gas, is a consequence of microbial fermentation in the digestive tract of livestock. Development of mitigation strategies to reduce CH 4 emissions from farmed animals is currently the subject of both scientific and environmental interest. Methanogens are the sole producers of ruminant CH 4 , and therefore CH 4 abatement strategies can either target the methanogens themselves or target the other members of the rumen microbial community that produce substrates necessary for methanogenesis. Understanding the relationship that methanogens have with other rumen microbes is crucial when considering CH 4 mitigation strategies for ruminant livestock. Genome sequencing of rumen microbes is an important tool to improve our knowledge of the processes that underpin those relationships. Currently, several rumen bacterial and archaeal genome projects are either complete or underway. Genome sequencing is providing information directly applicable to CH 4 mitigation strategies based on vaccine and small molecule inhibitor approaches. In addition, genome sequencing is contributing information relevant to other CH 4 mitigation strategies. These include the selection and breeding of low CH 4 -emitting animals through the interpretation of large-scale DNA and RNA sequencing studies and the modification of other microbial groups within the rumen, thereby changing the dynamics of microbial fermentation.Keywords: genome sequencing, methane mitigation, methanogens, rumen bacteria Implications Development of CH 4 mitigation strategies for ruminants without disrupting normal digestive function and reducing productivity is a major challenge. Genome sequencing is an effective way of gaining information on how rumen methanogens and bacteria interact and contribute to rumen function. This knowledge will be important when considering the design and implementation of ruminant CH 4 abatement strategies. Genomic information is already contributing to vaccine and small molecule inhibitor programmes that are aimed at reducing ruminant CH 4 emissions, but it will also underpin the analysis and comprehension of metagenomic sequence data sets, allowing the generation of testable hypotheses to gain a better understanding of rumen biology. IntroductionRuminants are foregut fermenters and have evolved an efficient digestive system in which microbes ferment plant fibre and provide fermentation end-products and other nutrients for growth of the animal (Clauss et al., 2010). Feed ingested by ruminants is fermented by a complex microbial community, which includes bacteria, ciliate protozoa, anaerobic fungi, archaea and viruses. The rumen is the first and largest foregut compartment and is the main site for microbial fermentation. The microbial ecology of the rumen has been the focus of numerous studies (reviewed by McSweeney and Mackie, 2012), but very little information is available regarding the microflora of the ruminant oral cavity and lower gastrointestinal tract. The rumen provides optimal conditio...

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New improved vaccines are needed for control of both bovine and human tuberculosis. Tuberculosis protein vaccines have advantages with regard to safety and ease of manufacture, but efficacy against tuberculosis has been difficult to achieve. Protective cellular immune responses can be preferentially induced when antigens are displayed on small particles. In this study, Escherichia coli and Lactococcus lactis were engineered to produce spherical polyhydroxybutyrate (PHB) inclusions which displayed a fusion protein of Mycobacterium tuberculosis, antigen 85A (Ag85A)-early secreted antigenic target 6-kDa protein (ESAT-6). L. lactis was chosen as a possible production host due its extensive use in the food industry and reduced risk of lipopolysaccharide contamination. Mice were vaccinated with PHB bead vaccines with or without displaying Ag85A-ESAT-6, recombinant Ag85A-ESAT-6, or M. bovis BCG. Separate groups of mice were used to measure immune responses and assess protection against an aerosol M. bovis challenge. Increased amounts of antigen-specific gamma interferon, interleukin-17A (IL-17A), IL-6, and tumor necrosis factor alpha were produced from splenocytes postvaccination, but no or minimal IL-4, IL-5, or IL-10 was produced, indicating Th1-and Th17-biased T cell responses. Decreased lung bacterial counts and less extensive foci of inflammation were observed in lungs of mice receiving BCG or PHB bead vaccines displaying Ag85A-ESAT-6 produced in either E. coli or L. lactis compared to those observed in the lungs of phosphate-buffered saline-treated control mice. No differences between those receiving wild-type PHB beads and those receiving recombinant Ag85A-ESAT-6 were observed. This versatile particulate vaccine delivery system incorporates a relatively simple production process using safe bacteria, and the results show that it is an effective delivery system for a tuberculosis protein vaccine. Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), infects a wide range of hosts, including domestic livestock and wildlife, and also causes TB in humans. Bovine TB poses a public health risk, particularly in regions where pasteurization of milk is not routine. This is of particular concern because more than 94% of the world's population lives in such regions, and M. bovis is the causative agent for up to 10% of TB cases in humans in these regions (14). Bovine TB also has a considerable economic impact on the agricultural industry. The human TB vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG) is only partially effective in both cattle and humans (2, 12). Development of an effective vaccine protecting against bovine TB would provide a cost-effective TB control strategy as well as have applicability for control of human TB caused by Mycobacterium tuberculosis.A number of new TB vaccines are entering human clinical trials, including recombinant BCG, virus-vectored vaccines, and recombinant protein vaccines (20). One of the major constraints in developing effective recombinant protein vaccines is t...