Novel vaccination strategies based on recombinant Mycobacterium bovis BCG

LKC Switzerland Ltd., Basel-Landschaft, Switzerland
International Journal of Medical Microbiology (Impact Factor: 3.61). 03/2003; 292(7-8):441-51. DOI: 10.1078/1438-4221-00227
Source: PubMed


In this manuscript, we will review the utilization of Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine against tuberculosis (TB) and as a carrier system for heterologous antigens. BCG is one of the most widely used vaccines. Novel techniques in genome manipulation allow the construction of virulence-attenuated recombinant (r)-BCG strains that can be employed as homologous vaccines, or as heterologous antigen delivery systems, for priming pathogen-specific immunity against infectious diseases, including TB. Several approaches are available for heterologous antigen expression and compartmentalization in BCG and recent findings show the potential to modulate and direct the immune responses induced by r-BCG strains as desired. Recent achievements in complete genome analysis of various target pathogens, combined with a better understanding of protective pathogen-specific immune responses, form the basis for the rational design of a new generation of recombinant mycobacterial vaccines against a multitude of infectious diseases.

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    • "Various clinical trials have demonstrated that BCG showed variable levels of efficacy against pulmonary TB. For example, a major trial in the United Kingdom showed >75% protection [3]; however, trials in south India and Malawi demonstrated that BCG failed to protect consistently against pulmonary TB [4,5]. The reasons for this have been a matter of debate and this indicates an urgent need for more effective vaccines to decrease the incidence of tuberculosis. "
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    ABSTRACT: Tuberculosis (TB) is one of the most prevalent cause of death due to a single pathogen. Bacillus Calmette Guérin (BCG) is the only vaccine available for clinical use that protects against miliary TB; however, this vaccine has shown variable levels of efficacy against pulmonary TB. In India, a single dose of BCG vaccine is given and there are few countries where repeated doses of BCG are given. The incidence of TB in India is very high inspite of primary vaccination in neonatal period and therefore requires consideration for repeated immunization. To improve BCG immunogenicity, we have evaluated specific antimycobacterial immune responses (anti-BCG IgG and IFN-gamma), T cell activity-ADA, CD4 and CD8 T cell count, and CD4/CD8 ratio in a peripheral blood mononuclear cells (PBMC) model using boost immunization protocols with the BCG vaccine. PBMC were induced with a repeat dose of BCG at 24 and 72 hrs of cell culture. At the end of the experimental time, supernatant was collected to estimate anti-BCG IgG titer, interferon gamma, ADA activity, CD 4 and CD8 T cell count, and CD4/CD8 ratio. We demonstrated that PBMC induced with a repeat dose of BCG showed an increased specific anti-mycobacterial immune responses, T cell activity, and ADA activity as compared to PBMC induced with BCG alone or without BCG induction. The repeat BCG stimulation of PBMC obtained from BCG vaccinated individuals shows enhanced immune activation with respect to increased anti-BCG titre, IFN-gamma and ADA activity without concomitant increase in CD4 and CD8 cells. This study provides some basic data in future experiments in animal models with respect to repeat BCG vaccination.
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    • "Recently, Wang et al. [48] tested the efficacy of recombinant Mycobacterium bovis BCG expressing ROP2 gene as a vaccine, using mouse experimental toxoplasmosis model. BCG, widely applied in immunoprophylaxis of tuberculosis, is a particularly attractive vector for delivering heterologous antigens because mycobacteria elicit TH1-mediated immune response without an additional adjuvant [49]. Vaccine ROP2-BCG induced strong specific humoral and cellular (IL-2 and IFN-γ in supernatants of splenocytes cell cultures) immunity. "
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