Comparative Immunology, Microbiology and Infectious Diseases
Bovine TB and the development of new vaccines
Section snippets
Introduction: Bovine tuberculosis—an overview
Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) and is also capable of infecting humans. In the 1930s, it was estimated that 15–20% of the UK cattle herd were infected with M. bovis. Around the same time, before the introduction of milk pasteurisation, it is reported that up to 6% of human TB deaths were due to M. bovis infection. The introduction of the skin test and slaughter policy to high incidence areas in the UK in the 1950s, followed by nationwide application of
Immune responses to Mycobacteria
Stimulation of the adaptive immune response of vertebrates by an antigen will induce the development of immunological memory in most cases. Upon re-exposure to the same antigen, the immune response will be faster and may also be of greater intensity, which may be crucial in the face of relatively fast replicating organisms, such as viruses or bacteria. Vaccination is based on the induction of immunological memory and successful vaccines induce appropriately biased, long-lived immune responses.
Requirements for a cattle TB vaccine
From a practical perspective, vaccinating cattle via injection would be easy and allow wide population coverage. Ideally a bTB vaccine would not only help to prevent transmission to other cattle but also prevent establishment of infection, which may be difficult to attain in all animals under a wide range of conditions. In addition, diagnostic tests that will allow the discrimination between vaccinated/protected and vaccinated/un-protected animals (differential diagnosis) are essential, with
Bacille Calmette Guerin (BCG)
The only potential vaccine currently available for bovine and human TB, M. bovis BCG, is unlikely to fulfil all of the criteria defined above for an ideal cattle vaccine. However, BCG remains the standard against which to judge the efficacy of any novel vaccines or strategies.
BCG was derived through serial passage of M. bovis on glycerol-soaked potato slices by Calmette and Guerin in 1921. Challenge experiments and field trials in cattle—as in human trials [79]—have demonstrated a high degree
Progress in developing cattle TB vaccines and vaccination strategies
Interestingly, the results obtained and conclusions reached in both the human and bovine TB vaccine research areas are very similar [78]. TB vaccine development programmes have largely been directed at replacing BCG. However, despite testing large numbers of vaccine candidates in small animal models most conferred significantly less protection than BCG and the degree of protection observed with some of these vaccines in cattle has been so far considerably lower than that observed with BCG (see
The future of TB vaccines
Early immune events are likely to be pivotal in determining the outcome of infectious challenge, and vaccination must stimulate appropriate immune responses. It is now well established that the major host cells for mycobacteria: MO and DC, display divergent responses to infection with mycobacteria. This response is likely dependent upon unique expression patterns of PRR by MO and DC. Early responses of DC dictate the nature of the subsequent adaptive immune response and as such, vaccines
Conclusions
Significant progress has been made in the development of TB vaccines for cattle. Most significantly, in parallel with developments in the human TB vaccine development field, vaccine strategies are now being considered for supplementing rather than replacing BCG vaccination. In particular, subunit vaccines based on DNA or proteins in adjuvant used in combination with BCG have resulted in better protection against experimental challenge with M. bovis than BCG vaccination on its own. BCG
Acknowledgement
The authors were funded by the Department for Environment, Food and Rural Affairs, United Kingdom and Biotechnology and Biological Sciences Research Council, UK.
References (149)
- et al.
The effect of repeated tuberculin skin testing of cattle on immune responses and disease following experimental infection with Mycobacterium bovis
Vet Immunol Immunopathol
(2004) Evasion of host cell defense mechanisms by pathogenic bacteria
Curr Opin Immunol
(2001)- et al.
Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages
Cell Immunol
(2000) - et al.
From synapses to immunological memory: the role of sustained T cell stimulation
Curr Opin Immunol
(2000) - et al.
Interaction of antigen presenting cells with mycobacteria
Vet Immunol Immunopathol
(2004) Biology of natural killer cells
Adv Immunol
(1989)- et al.
Reference values for relative numbers of natural killer cells in cattle blood
Dev Comp Immunol
(2004) - et al.
Age-related changes in human blood lymphocyte subpopulations
J Pediatrics
(1992) - et al.
NK-DC interaction: on the usefulness of auto-aggression
Autoimmunity Rev
(2005) - et al.
Role of T cell subsets in immunity against intracellular bacteria: experimental infections of knock-out mice with Listeria monocytogenes and Mycobacterium bovis BCG
Immunobiology
(1994)
Analysis of the antigen-specific IFN-gamma producing T-cell subsets in cattle experimentally infected with Mycobacterium bovis
Vet Immunol Immunopathol
Lymphocyte subtypes in experimentally induced early-stage bovine tuberculous lesions
J Comp Pathol
A second experiment to challenge the resistance to tuberculosis in BCG vaccinated cattle in Malawi
Brit Vet J
The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection
Cell
Immunological responses and protection against Mycobacterium bovis in calves vaccinated with a low dose of BCG
Vaccine
Protection of cattle from bovine tuberculosis by vaccination with BCG by the respiratory or subcutaneous route, but not by vaccination with killed Mycobacterium vaccae
Res Vet Sci
Vaccination with DNA vaccines encoding MPB70 or MPB83 or a MPB70 DNA prime-protein boost does not protect cattle against bovine tuberculosis
Tuberculosis (Edinb)
Effect of different adjuvants on the immune responses of cattle vaccinated with Mycobacterium tuberculosis culture filtrate proteins
Vet Immunol Immunopathol
Vaccination of cattle against Mycobacterium bovis
Tuberculosis (Edinb)
Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6
Vaccine
Use of the bovine model of tuberculosis for the development of improved vaccines and diagnostics
Tuberculosis
A second experiment to challenge the resistance to tuberculosis in BCG vaccinated cattle in Malawi
Brit Vet J
Variation in protection by BCG: implications of and for heterologous immunity
Lancet
How environmental mycobacteria may predetermine the protective efficacy of BCG
Tubercle
Lack of evidence for a reduction in the efficacy of subcutaneous BCG vaccination in mice infected with nontuberculous mycobacteria
Tubercle
Zoonotic tuberculosis due to Mycobacterium bovis in developing countries
Emerg Infect Dis
Bovine tuberculosis in cattle and badgers
A sequential study of the bovine tuberculin reaction
Immunology
Mycobacterium bovis infection and control in domestic livestock
Rev Sci Technol
Development of vaccines for bovine tuberculosis
Tuberculosis: latency and reactivation
Infect Immun
A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival
Proc Natl Acad Sci USA
Nonopsonic phagocytosis of zymosan and Mycobacterium kansasii by CR3 (CD11b/CD18) involves distinct molecular determinants and is or is not coupled with NADPH oxidase activation
Infect Immun
The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages
Infect Immun
Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response
J Immunol
Mycobacterium tuberculosis induces differential cytokine production from dendritic cells and macrophages with divergent effects on naive T cell polarization
J Immunol
Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response
J Immunol
Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis
J Immunol
Dendritic cells and the control of immunity
Nature
The dendritic cell system and its role in immunogenicity
Annu Rev Immunol
Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells
Eur J Immunol
Interaction of dendritic cells with mycobacteria: where the action starts
Immunol Cell Biol
IFN-alpha beta released by Mycobacterium tuberculosis-infected human dendritic cells induces the expression of CXCL10: selective recruitment of NK and activated T cells
J Immunol
DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells
J Exp Med
Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin: involvement of toll-like receptors
Infect Immun
Activation of human dendritic cells following infection with Mycobacterium tuberculosis
J Immunol
Enhanced antigen-presenting activity and tumour necrosis factor-alpha-independent activation of dendritic cells following treatment with Mycobacterium bovis bacillus Calmette-Guerin
Immunology
The functional changes in antigen presenting cells following infection with virulent and avirulent Mycobacterium bovis
Bacterial metabolism, cytokine mRNA transcription and viability of bovine alveolar macrophages infected with Mycobacterium bovis BCG or virulent M. bovis
Immunol Cell Biol
Immune responses induced in cattle by virulent and attenuated Mycobacterium bovis strains: correlation of delayed-type hypersensitivity with ability of strains to grow in macrophages
Infect Immun
Cited by (31)
Rapid molecular diagnosis of live Mycobacterium tuberculosis on an integrated microfluidic system
2022, Sensors and Actuators B: ChemicalConventional and molecular determination of drug resistance in Mycobacterium tuberculosis and Mycobacterium bovis isolates in cattle
2019, TuberculosisCitation Excerpt :Though M. tuberculosis and M. bovis were isolated from TB like lesions in cattle, the ability of M. tuberculosis to transmit the same between animals or to human beings has not been proved. Effective BTB vaccines are also not currently available [10]. Attempts to treat with anti-tuberculosis drugs are providing controversial results [11].
Mycobacterium bovis-infected macrophages from resistant and susceptible cattle exhibited a differential pro-inflammatory gene expression profile depending on strain virulence
2016, Veterinary Immunology and ImmunopathologyCitation Excerpt :In developed countries, eradication programs have reduced or eliminated BT, however reservoirs in wildlife can make eradication difficult. BT is still common in less developed countries causing great economic losses due to low production and trade restrictions (Hope and Villarreal-Ramos, 2008; Müller et al., 2013; Shu et al., 2014). The course of the infection and its epidemiological consequences depend upon a complex interplay of host, environmental and bacterial factors.
Multiple β-defensin genes are upregulated by the vitamin D pathway in cattle
2015, Journal of Steroid Biochemistry and Molecular BiologyComparison of gene expression of immune mediators in lung and pulmonary lymph node granulomas from cattle experimentally infected with Mycobacterium bovis
2014, Veterinary Immunology and Immunopathology