Effectiveness of BCG vaccination to aged mice
© Ito et al; licensee BioMed Central Ltd. 2010
Received: 13 June 2010
Accepted: 1 September 2010
Published: 1 September 2010
The tuberculosis (TB) still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG) is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB) make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice.
The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old) were comparable to those of young mice (4- to 6-week-old). The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice.
These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.
The number of aged people has been increasing all over the world. World health organization reported that the increase rate of the number was 28% in the recent decade (2000 to 2009), and predicted that the number would reach 1.5 billion by 2050 . The largest population of aged people (predicted to be 78% by the year 2050) resides in developing countries , where many infectious diseases, including tuberculosis (TB) , are endemic. Given the increased susceptibility of the elderly to infectious diseases, the rapid rise in the elderly population will become a significant threat to global health care.
The current TB vaccine is the live attenuated bacterium Mycobacterium bovis Bacillus Calmette Guérin (BCG). BCG is known to protect against tuberculous meningitis in babies children. However, it does not efficiently and consistently protect against pulmonary TB in adults. Over the years, many hypotheses have been put forward to explain the apparent variability in the protective efficacy of BCG, which varies from 0 to 80% . Explanations for this inconsistency include differences in trial methodology, host population genetics, use of different BCG vaccine strains , and heterogeneous immunity to a variety of environmental mycobacteria that may interfere with the protection provided by BCG [5, 6]. We have previously reported that 'early shared BCG strains' (ex. BCG-Russia, BCG-Moreau, BCG-Japan), which are chronologically early strains distributed form Pasteur Institute, conserve the characteristics of authentic BCG vaccine [7, 8]. Immune response profiles following BCG vaccination comprise myriads of effecter mechanisms, multiple T-cell subsets, and many targeted antigens. BCG is capable of inducing Th1 responses , which are critical for protection against mycobacterial infection .
As an individual ages, significant immunological changes occur, which contribute to the enhanced morbidity and mortality associated with infectious diseases in the elderly. After puberty, thymic atrophy leads to a progressive decrease in the output of naïve T cells and decreased diversity in the T-cell repertoire . CD8+ T cells play an important role in innate response to pathogen such as M. tuberculosis in the aged mouse [12, 13]. In this study, the efficacy of vaccination with BCG in aged mice was investigated.
Results and Discussion
T cell subsets in the peripheral blood of young and aged mice a
12.9 ± 6.55
17.3 ± 9.23
1.33 ± 0.66
5.5 ± 1.83
6.2 ± 0.37
0.56 ± 0.28
In order to avoid the effects of cytokines induced by BCG vaccination on infection of M. tuberculosis, the levels of cytokines (IL-6, IL-10, IL-12p70, monocyte chemotactic protein (MCP)-1, IFN-γ, tumor necrosis factor (TNF)-α) in the serum from BCG vaccinated young mice were measured by Cytometric Beads Array (CBA) system (BD Biosciences, San Jose, CA). IL-10, IL-12 p70 and IFN-γ increased at 1 week post-inoculation, and returned to the basal level at 2 to 4 weeks. IL-6, TNF, MCP-1 peaked at two weeks after inoculation, and returned to the basal level at 4 weeks (data not shown). Therefore, the infection experiments were conducted six weeks after inoculation.
In conclusion, this is a first report to evaluate the efficacy of BCG vaccination in aged (24-month-old) mice as compared to young (4- to 6-week-old) mice. BCG inoculation induced Th1 type immune responses in both young and aged mice (Figure 1). The protection activity was observed in aged mice, which was comparable to young mice (Figure 2). Our study suggests that vaccination in aged people could be effective to prevent infection against tuberculosis.
Mycobacterium bovis Bacillus Calmette Guérin
monocyte chemotactic protein
tumor necrosis factor
colony forming unit
purified protein derivatives.
This work was supported in part by Grant-in-Aid for Scientific Research on Kiban C from The Ministry of Education, Science, Sports, and a grant for Research on Publicly Essential Drugs and Medical Devices, KHC1021, KHC1016, from the Japan Health Sciences Foundation. We are grateful to Center for Experimental Animal Science, Nagoya City University Graduate School of Medical Sciences supporting the experiments involving the husbandry and management of laboratory animals.
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