• Users Online: 124
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
EDITORIAL
Year : 2014  |  Volume : 3  |  Issue : 1  |  Page : 1-4

How to avoid the impact of environmental mycobacteria towards the efficacy of BCG vaccination against tuberculosis?


Department of Immunology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India

Date of Web Publication24-Feb-2017

Correspondence Address:
Om Parkash
Department of Immunology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.ijmyco.2014.01.006

Rights and Permissions
  Abstract 


Bacillus Calmette–Guérin (BCG) remains the only widely used vaccine against tuberculosis (TB). Consistent efficacy has been proved in infants but not in adults from developing countries. Epidemiological and experimental studies have pointed out that, prior exposure to prevailing environmental mycobacteria could be responsible for the poor efficacy of BCG as an anti-TB vaccine in adults living in developing countries. Sensitization by environmental mycobacteria may down-modulate the immunologic behavior of BCG on the one hand and may mask its efficacy on the other hand. Some of the important deciding factors for poor efficacy of BCG, due to exposure of the subjects to prevailing environmental mycobacteria, are thought to be (i) Life stage: neonatus versus adolescence; (ii) shared antigens between prevailing environmental mycobacteria and BCG; and (iii) generation of cross-reactive T-regulatory cells against environmental mycobacteria and BCG. In this communication, some novel strategies have been discussed for countering the down modulating impact of environmental mycobacteria towards performance of BCG as an anti-TB vaccine.

Keywords: Tuberculosis, BCG, Vaccine, Environmental mycobacteria, Immunoprophylaxis


How to cite this article:
Parkash O. How to avoid the impact of environmental mycobacteria towards the efficacy of BCG vaccination against tuberculosis?. Int J Mycobacteriol 2014;3:1-4

How to cite this URL:
Parkash O. How to avoid the impact of environmental mycobacteria towards the efficacy of BCG vaccination against tuberculosis?. Int J Mycobacteriol [serial online] 2014 [cited 2022 Jan 18];3:1-4. Available from: https://www.ijmyco.org/text.asp?2014/3/1/1/200920




  Introduction Top


Tuberculosis (TB) caused by Mycobacterium tuberculosis is a major global health problem, causing more than 1.3 million deaths every year [1]. The most effective and economic way of controlling this problem would be the availability of an effective vaccine. Bacillus Calmette–Guérin, known as BCG in the abbreviated form, is an attenuated form of Mycobacterium bovis which was isolated by Albert Calmette and Camille Guérin nearly a century ago and highly resembles M. tuberculosis [2]. The use of BCG for human vaccination against TB was initiated in 1921 and to date there is no alternate of this vaccine. Immunologically, BCG is known to generate T-cell helper type-1 (Th1) immunity for protection of the host from M. tuberculosis infection [3]. As documented, BCG has been found to be significantly protective against severe forms (disseminating and meningeal) of TB in children; however, its efficacy in adults is inconsistent and varies from 0–80% in different geographical regions [3],[4]. Moreover, there are evidences of exacerbated disease in certain vaccinated individuals. Nevertheless, BCG is still being used worldwide for vaccination against TB despite foregoing drawbacks. The poor performance of BCG in developing countries, where rates of TB are much higher, is very discouraging. The reasons why BCG is not very effective in immunocompetent individuals are considered to be: strain differences in BCG, prevalence of environmental mycobacteria, genetics of host, nutritional factors and presence of helminthes co-infections, etc. [5]. Among the various reasons for poor efficacy of BCG in immunocompetent individuals, prior exposure to environmental mycobacteria is thought to be an important and widely accepted cause of poor efficacy of BCG vaccine in adults from developing countries [3],[6],[7],[8],[9],[10]. This study discusses how the environmental mycobacteria may contribute towards yielding weak efficacy of BCG as an anti-TB vaccine. Also, this study describes possible strategies to overcome such down-modulating impacts towards performance of BCG as a vaccine.


  BCG and its efficacy in neonates versus adults Top


BCG has been reported to be significantly effective in children when it is delivered in the neonatal stage at birth and the magnitude of specific CD4+ T cells peaks 6–10 weeks after vaccination [3]. It is well-documented that in addition to immunizing the Th1 cells, BCG is known to act as an immunomodulator [11],[12],[13] as well. Though BCG primarily induces Th1-type of immune response [3], depending upon antigen and cytokine milieu, BCG may also induce Th2-like immune response [14],[15]. At the neonatal stage, the immune system is considered to be immature, and along with aging, progressive maturation of the immune system occurs due to persistent exposure to antigens present in the surroundings [16],[17],[18]. In neonates, the naïve Th0 cells are abundant [19] and along with maturation of the immune system, these cells switch towards Th1 or Th2. Since exposure of the immune system to environmental mycobacteria is expected to be less in neonates when compared with adults, down-modulation of the BCG efficacy by environmental mycobacteria would be lower at the neonatal stage. Hence, during the developmental stage of the immune system in the neonates, exposure to vaccinated BCG may play a pivotal role in switching the naïve Th cell towards Th1. On the other hand, adults have a mature immune system and almost an established Th1/Th2 profile. When compared with adults, the better efficacy [20] of BCG in infants/children might be due to more intense switching of the immune system towards Th1 during the neonatal stage. This all could be due to immunomodulating as well as immunizing behavior of BCG at the level of Th1.

Regarding adults, the efficacy of BCG has been reported to be lower in the developing countries [3] where most of the people from the neonatal stage onwards live in an environment where mycobacteria are highly prevalent. Hence, along with aging as well as persistent exposure to mycobacteria, a consistent evocation of the Th1-mediated immunity occurs. Of course, the total period of exposure of the adults to environmental mycobacteria remains more than the time span needed for growth of a neonate to a child. During such a time span of about 15 years for reaching the neonate to adolescence stage, the immune response involving shift (due to environmental mycobacteria) of Th0/Th2 to Th1 might reach a threshold where subsequent vaccination with BCG may not show a significant difference in protection between the non-vaccinated and vaccinated groups. As a result thereof, it is reflected as if efficacy of BCG vaccine is weak or the vaccine is non-effective. The same has been explained by two hypotheses [3]: (i) blocking hypothesis: due to cell-mediated immunity generated by exposure of the host to the prevailing environmental mycobacteria, BCG delivered to the host might be killed. This may result in limiting the available BCG-derived antigens from further evoking the immune system. Thereby, a diminished immunity, against M. tuberculosis, in the host is generated. It is called blocking effect of environmental mycobacteria towards BCG efficacy; and (ii) masking hypothesis: it is a phenomenon where the background immunity generated due to prior exposure of individuals to environmental mycobacteria masks the efficacy of subsequent BCG vaccination. As a result thereof, it is reflected as if efficacy of the BCG vaccine is weak or the vaccine is non-effective.


  Possible role of T-regulatory cells on efficacy of BCG Top


T-regulatory (Treg) cells [21] are subtypes of CD4+ T-helper cells that are known to regulate the immune system by suppressing the proliferation of lymphocytes, the production of cytokines and the production of antibodies. Primarily, there are two subsets of regulatory cells: (i) adaptive – such Treg cells are induced in the periphery due to stimulation by prevailing sub-optimal levels of antigens; and (ii) natural – these are derived from thymus and already have immune-suppressing capability. Induced Treg cells are again of two types: (i) iTr cells which have suppressive action by releasing IL-10; and (ii) Th3 cells which act by releasing TGF-β, an immunosuppressive cytokine. Treg cells also act through cell–cell contact where CTLA-4 (cytotoxic lymphocyte associated antigen-4) present on Treg cells modulates functions of antigen-presenting dendritic cells, through binding to CD80 and/or CD86 molecules on antigen presenting cells. This results in inhibition of maturation, down-regulation of CD80/CD86, and induction of immunoregulatory enzyme indoleamine-2,3-desoxygenase which transmits an inhibitory signal to T-cells. Also, Treg cells compete with effector CD4+ T-cells for interaction with antigen-captured antigen-presenting cells [22].

Currently, the vaccine immunogenicities are analyzed keeping possible involvement of Treg cells towards dampening of their efficacies. In the context of the anti-TB vaccine, the environmental mycobacteria are considered to weaken the efficacy of BCG. There is information describing the induction of Treg cells by environmental mycobacteria [8],[23],[24]. The sensitised Treg cells generated by such antigens are thought to be stimulated by vaccinated BCG which in turn may dampen the immune response generated by BCG through inhibiting the T-cell effector functions [8]. Additionally, BCG itself has also been reported to be involved in the generation of Treg cells [25],[26],[27]. Priming the host with BCG vaccine followed by boosting with Treg down-regulating mycobacterial proteins has been reported to be promising [28],[29]. This further supports implication of Treg cells in down-modulating the efficacy of BCG as a vaccine. However, attenuation of Treg concomitant to immunization with BCG and before immunization with BCG did not improve the vaccine outcome [25],[30]. These findings also point out that Treg cells generated after BCG vaccination may play a role in suppressing the anti-TB efficacy of BCG vaccine. Treg cells are known to be produced during M. tuberculosis infection as well [31],[32], which may play an important role in TB pathogenesis [33],[34],[35],[36],[37],[38] and also in further dampening the BCG immunizing capacity [30],[39] against TB. Thus, the Treg cells have suppression effect on the efficacy of BCG at three different levels described in the foregoing. It is speculated that pre-exposure to mycobacterial antigens (present in environmental mycobacteria) may induce and sensitize the Treg cells in the host. These sensitized cells may further be stimulated by vaccination with BCG and subsequently by M. tuberculosis infection. Eventually, all this may result in the generation of a larger pool of Treg cells which in turn could influence the BCG vaccine efficacy [24]. Keeping all of this information in view, it is worth mentioning that the generation of Treg cells by environmental mycobacteria may initiate the process leading towards down-modulation of the efficacy of the BCG vaccine.


  Perspectives Top


The foregoing discussion points out that, probably, shared antigens between environmental mycobacteria and BCG may be responsible for blocking as well as masking the effect towards immunizing the efficiency of the anti-TB vaccine. Such effects due to environmental mycobacteria may not occur only with conventional BCG; rather, they may be noticed even with genetically engineered BCG as well. This study suggests two remedies ([Figure 1]) that may help in unravelling the factual efficacy of BCG vaccines and in improving the performance of anti-TB vaccines respectively: (i) the testing of candidate BCG vaccines must be conducted with the people living in the regions where prevalence of environmental mycobacteria may be negligible. Doing so would eliminate the blocking and masking effects of environmental mycobacteria; and (ii) genes encoding only those proteins that may be present in BCG as well as M. tuberculosis but absent in environmental mycobacteria may be selected through genomic comparisons of the concerned mycobacterial species. Employing the selected desirable genes, the corresponding antigens may be produced by genetic engineering. In case such proteins are found to be immunologically potential, then they may prove to be promising antigens for anti-TB vaccines as they would be devoid of the undesirable down-modulating and masking effects of environmental mycobacteria.
Figure 1: Strategies for avoiding the impact of environmental mycobacteria (EM) on efficacy of BCG as a vaccine against tuberculosis.

Click here to view


Keeping in view the possible role of Treg cells towards weakening the efficacy of the BCG vaccine, this write-up suggests that ([Figure 1]): (i) Strategies to modulate the Treg cell-mediated down-modulating effect on Th1 cells to weaken the efficacy BCG need to be developed, perhaps on the lines described elsewhere [40]; (ii) Identifying Treg cell-inducing BCG antigens is worth attempting. By identifying immunosuppressive antigens, better BCG vaccines might be created by dissecting out Treg cell-inducing proteins from BCG. Development of such deficient versions of BCG for Treg cell-inducing proteins may be carried out by genetic manipulation of BCG genes through disruption or deletion of concerned genes; And (iii) Developing recombinant BCG (rBCG) strains expressing Treg down-regulating antigens might stimulate more potent immune responses against M. tuberculosis infection.

Most likely, these suggested strategies may lead towards the bettering of BCG as an anti-TB vaccine. Nonetheless, whatever may be the strategy to improve the performance of BCG through reducing the Treg population, the ratio of Th1-type of CD4 cells (through which BCG acts) and Treg cells should be maintained at such a level so that tissue damage might be low with high efficacy of the BCG vaccine.


  Conflict of interest Top


There is no conflict of interest regarding this manuscript.


  Acknowledgements Top


Thanks to Infolep, Amsterdam, The Netherlands, for helping in providing the scientific literature. Thanks to Juraj Ivanyi, Department of Oral Medicine & Pathology, Guy's Campus, Medical and Dental Schools of Kings College, London, United Kingdom. Thanks to Ms Sonali Agrawal for helping in preparing the sketch diagram. Thanks to Indian Council of Medical Research for routine support.



 
  References Top

1.
World Health Organization, Global Tuberculosis Control, WHO Report 2013, 2013.  Back to cited text no. 1
    
2.
S. Luca, T. Mihaescu, History of BCG vaccine, Maedica (Buchar) 8 (2013) 53–58.  Back to cited text no. 2
    
3.
P. Andersen, T.M. Doherty, The success and failure of BCG – implications for a novel tuberculosis vaccine, Nat. Rev. Microbiol. 3 (2005) 656–662.  Back to cited text no. 3
    
4.
P.E. Fine, Variation in protection by BCG: implications of and for heterologous immunity, Lancet 346 (1995) 1339–1345.  Back to cited text no. 4
    
5.
T.H. Ottenhoff, S.H. Kaufmann, Vaccines against tuberculosis: where are we and where do we need to go?, PLoS Pathog 8 (2012) e1002607.  Back to cited text no. 5
    
6.
P.E. Fine, S. Floyd, J.L. Stanford, P. Nkhosa, A. Kasunga, S. Chaguluka, et al, Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy, Epidemiol. Infect. 126 (2001) 379–387.  Back to cited text no. 6
    
7.
L. Brandt, J. Feino Cunha, A. Weinreich Olsen, B. Chilima, P. Hirsch, R. Appelberg, et al, Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis, Infect. Immun. 70 (2002) 672–678.  Back to cited text no. 7
    
8.
P. Ho, X. Wei, G.T. Seah, Regulatory T cells induced by Mycobacterium chelonae sensitization influence murine responses to bacille Calmette–Guerin, J. Leukoc. Biol. 88 (2010) 1073–1080.  Back to cited text no. 8
    
9.
T.P. Primm, C.A. Lucero, J.O. Falkinham 3rd, Health impacts of environmental mycobacteria, Clin. Microbiol. Rev. 17 (2004) 98–106.  Back to cited text no. 9
    
10.
R.E. Weir, G.F. Black, B. Nazareth, S. Floyd, S. Stenson, C. Stanley, et al, The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to Bacille Calmette–Guérin vaccination in southern England and northern Malawi, Clin. Exp. Immunol. 146 (2006) 390–399.  Back to cited text no. 10
    
11.
E.K. Vetskova, M.N. Muhtarova, T.I. Avramov, T.R. Stefanova, I.J. Chalakov, M.H. Nikolova, Immunomodulatory effects of BCG in patients with recurrent respiratory papillomatosis, Folia Med. (Plovdiv) 55 (2013) 49–54.  Back to cited text no. 11
    
12.
B. Tomov, D. Popov, R. Tomova, N. Vladov, W. DEN Otter, Z. Krastev, Therapeutic response of untreatable hepatocellular carcinoma after application of the immune modulators IL-2, BCG and melatonin, Anticancer Res. 33 (2013) 4531–4535.  Back to cited text no. 12
    
13.
N.M. Gandhi, A. Morales, D.L. Lamm, Bacillus Calmette– Guérin immunotherapy for genitourinary cancer, BJU Int. 112 (2013) 288–297.  Back to cited text no. 13
    
14.
A. Martino, A. Sacchi, N. Sanarico, F. Spadaro, C. Ramoni, A. Ciaramella, et al, Dendritic cells derived from BCG-infected precursors induce Th2-like immune response, J. Leukoc. Biol. 76 (2004) 827–834.  Back to cited text no. 14
    
15.
Y. Djuardi, E. Sartono, H. Wibowo, T. Supali, M. Yazdanbakhsh, A longitudinal study of BCG vaccination in early childhood: the development of innate and adaptive immune responses, PLoS One 5 (2010) e14066.  Back to cited text no. 15
    
16.
C.F. Inman, K. Haverson, S.R. Konstantinov, P.H. Jones, C. Harris, H. Smidt, et al, Rearing environment affects development of the immune system in neonates, Clin. Exp. Immunol. 160 (2010) 431–439.  Back to cited text no. 16
    
17.
M. Lappalainen, Environmental microbes and immunological development in children – the role of animal, bacterial and fungal exposures (Ph.D. thesis), National Institute for Health and Welfare (THL), Helsinki, Finland, 2010.  Back to cited text no. 17
    
18.
S.T. Kelley, J.A. Gilbert, Studying the microbiology of the indoor environment, Genome Biol. 14 (2013) 202.  Back to cited text no. 18
    
19.
C. Gaetano, Development of the immune system in neonates, J. Arab. Neonatal Forum 2 (2005) 5–11.  Back to cited text no. 19
    
20.
B.B. Trunz, P. Fine, C. Dye, Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of costeffectiveness, Lancet 367 (2006) 1173–1180.  Back to cited text no. 20
    
21.
K.H. Mills, Regulatory T cells: friend or foe in immunity to infection?, Nat Rev. Immunol. 4 (2004) 841–855.  Back to cited text no. 21
    
22.
T. Nishimoto, M. Kuwana, CD4+CD25+Foxp3+ regulatory T cells in the pathophysiology of immune thrombocytopenia, Semin. Hematol. 50 (2013) S43–s49.  Back to cited text no. 22
    
23.
C. Zuany-Amorim, E. Sawicka, C. Manlius, A. Le Moine, L.R. Brunet, D.M. Kemeny, et al, Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergenspecific regulatory T-cells, Nat. Med. 8 (2002) 625–629.  Back to cited text no. 23
    
24.
M.M. Coleman, J. Keane, K.H. Mills, Editorial: tregs and BCG– dangerous liaisons in TB, J. Leukoc. Biol. 88 (2010) 1067–1069.  Back to cited text no. 24
    
25.
Q. Li, H.H. Shen, Neonatal bacillus Calmette–Guérin vaccination inhibits de novo allergic inflammatory response in mice via alteration of CD4+CD25+ T-regulatory cells, Acta Pharmacol. Sin. 30 (2009) 125–133.  Back to cited text no. 25
    
26.
Y.J. Kim, H.J. Kim, M.J. Kang, H.S. Yu, J.H. Seo, H.Y. Kim, et al, Bacillus Calmette–Guérin suppresses asthmatic responses via CD4+CD25+ regulatory T cells and dendritic cells, Allergy Asthma Immunol. Res. 5 (2012) e196.  Back to cited text no. 26
    
27.
G. Laćan, H. Dang, B. Middleton, M.A. Horwitz, J. Tian, W.P. Melega, et al, Bacillus Calmette–Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine mouse model of Parkinson's disease, J. Neurosci. Res. 91 (2013) 1292–1302.  Back to cited text no. 27
    
28.
Y. Luo,W. Jiang, Z. Da, B.Wang, L. Hu, Y. Zhang, et al, Subunit vaccine candidate AMM down-regulated the regulatory T cells and enhanced the protective immunity of BCG on a suitable schedule, Scand. J. Immunol. 75 (2012) 293–300.  Back to cited text no. 28
    
29.
P.F. Fedatto, C.A. Sérgio, M.O. Paula, A.F. Gembre, L.H. Franco, P.F. Wowk, et al, Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4(+)/CD4(+) Foxp3(+) cells, Immunology 137 (2012) 239–248.  Back to cited text no. 29
    
30.
B. Jaron, E. Maranghi, C. Leclerc, L. Majlessi, Effect of attenuation of Treg during BCG immunization on antimycobacterial Th1 responses and protection against Mycobacterium tuberculosis, PLoS One 3 (2008) e2833.  Back to cited text no. 30
    
31.
J.M. Hougardy, S. Place, M. Hildebrand, A. Drowart, A.S. Debrie, C. Locht, et al, Regulatory T-cells depress immune responses to protective antigens in active tuberculosis, Am. J. Respir. Crit. Care Med. 4 (2007) 409–416.  Back to cited text no. 31
    
32.
N.D. Marin, S.C. París, V.M. Vélez, C.A. Rojas, M. Rojas, L.F. García, Regulatory T cell frequency and modulation of IFNgamma and IL-17 in active and latent tuberculosis, Tuberculosis (Edinb) 90 (2010) 252–261.  Back to cited text no. 32
    
33.
P.K. Sharma, P.K. Saha, A. Singh, S.K. Sharma, B. Ghosh, D.K. Mitra, FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis, Am. J. Respir. Crit. Care Med. 179 (2009) 1061–1070.  Back to cited text no. 33
    
34.
X. Chen, B. Zhou, M. Li, Q. Deng, X. Wu, X. Le, C. Wu, et al, CD4(+)CD25(+)FoxP3(+) regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease, Clin. Immunol. 123 (2007) 50–59.  Back to cited text no. 34
    
35.
V. Guyot-Revol, J.A. Innes, S. Hackforth, T. Hinks, A. Lalvani, Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis, Am. J. Respir. Crit. Care Med. 173 (2006) 803–810.  Back to cited text no. 35
    
36.
R. Ribeiro-Rodrigues, Co.T. Resende, R. Rojas, Z. Toossi, R. Dietze, W.H. Boom, et al, A role for CD4+ CD25+ T cells in regulation of the immune response during human tuberculosis, Clin. Exp. Immunol. 144 (2006) 25–34.  Back to cited text no. 36
    
37.
L. Li, S.H. Lao, C.Y. Wu, Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients, Tuberculosis (Edinb) 87 (2007) 526–534.  Back to cited text no. 37
    
38.
L. Li, C.Y. Wu, CD4+ CD25+ Treg cells inhibit human memory gamma delta T cells to produce IFN-gamma in response to M. tuberculosis antigen ESAT-6, Blood 111 (2008) 5629–5636.  Back to cited text no. 38
    
39.
H.A. Fletcher, A.A. Pathan, T.K. Berthoud, S.J. Dunachie, K.T. Whelan, N.C. Alder, et al, Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-beta1, Vaccine 26 (2008) 5269–5275.  Back to cited text no. 39
    
40.
S. Nandakumar, C.W. Miller, U. Kumaraguru, T regulatory cells: an overview and intervention techniques to modulate allergy outcome, Clin. Mol. Allergy. 7 (2009) 5.  Back to cited text no. 40
    


    Figures

  [Figure 1]


This article has been cited by
1 Bacille Calmette-Guérin: An Ophthalmic perspective
Manish Jain,Julie Vadboncoeur,Sunir J. Garg,Jyotirmay Biswas
Survey of Ophthalmology. 2021;
[Pubmed] | [DOI]
2 BCG-mediated protection against M. tuberculosis is sustained post-malaria infection independent of parasite virulence
Emily Tangie, Avril Walters, Nai-jen Hsu, Michelle Fisher, Stefan Magez, Muazzam Jacobs, Roanne Keeton
Immunology. 2021;
[Pubmed] | [DOI]
3 The burden of mycobacteria species among children from postvaccination abscess in Southern India
Kannaiyan Kavitha, Latha Ragunathan, Paramasivam Elantheriyan, Kuppusamy Gopalakrishnan, KumaraswamyAjay Gopala, IndrajithDevandra Balamurugan, RagunadhaReddy Navya, SherinSamuel Marcella, GobichettipalayamKanniappan Venkatachalam
International Journal of Mycobacteriology. 2021; 10(4): 358
[Pubmed] | [DOI]
4 Vaccine Potential of Mycobacterial Antigens against Asthma
Abu Salim Mustafa
Medical Principles and Practice. 2020; 29(5): 404
[Pubmed] | [DOI]
5 Disseminated BCG Infection and Primary Immunodeficiencies: A Report from Two Tertiary Centers
Shima Baradaran,Zahra Chavoshzadeh,Roxana Ghanaie,Seyed Alireza Mahdaviani,Sepideh Darougar,Mehrnaz Mesdaghi,Seyed Alireza Fahimzad,Sedigheh Rafiei Tabatabaei,Abdollah Karimi,Shahnaz Armin,Mahboubeh Mansouri,Delara Babaie
Archives of Clinical Infectious Diseases. 2019; In Press(In Press)
[Pubmed] | [DOI]
6 Measuring autophagy level along with vaccine reactive IFN-?+CD4+ Th1 cells may be a promising approach to understand effi cacy of anti TB vaccine(s)
Parkash Om
Journal of Vaccines and Immunology. 2018; : 001
[Pubmed] | [DOI]
7 BCG and protection against inflammatory and auto-immune diseases
Magdalena Kowalewicz-Kulbat,Camille Locht
Expert Review of Vaccines. 2017; : 1
[Pubmed] | [DOI]
8 T regulatory cells: Achilles’ heel of Mycobacterium tuberculosis infection?
Om Parkash,Sonali Agrawal,M. Madhan Kumar
Immunologic Research. 2015; 62(3): 386
[Pubmed] | [DOI]
9 Radiologic manifestations of pulmonary tuberculosis in patients of intensive care units
Seyed MohammadReza Hashemian,Payam Tabarsi,Mehrdad Bakhshayesh Karam,Shahram Kahkouee,Majid Marjani,Hamidreza Jamaati,Nazila Shekarchi,Seyed Amir Mohajerani,Ali Akbar Velayati
International Journal of Mycobacteriology. 2015; 4(3): 233
[Pubmed] | [DOI]
10 T Regulatory Cells and BCG as a Vaccine against Tuberculosis: An Overview
Om Parkash
World Journal of Vaccines. 2015; 05(02): 96
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
BCG and its effi...
Possible role of...
Perspectives
Conflict of interest
Acknowledgements
References
Article Figures

 Article Access Statistics
    Viewed1537    
    Printed36    
    Emailed0    
    PDF Downloaded120    
    Comments [Add]    
    Cited by others 10    

Recommend this journal