Boosting BCG with MVA85A: The first candidate subunit vaccine for tuberculosis in clinical trials

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Tuberculosis (Impact Factor: 2.71). 03/2005; 85(1-2):47-52. DOI: 10.1016/
Source: PubMed


There is an urgent need for an improved vaccine against tuberculosis. Heterologous prime-boost immunization regimes induce higher levels of cellular immunity than homologous boosting with the same vaccine. Using BCG as the priming immunization in such a regime allows for the retention of the beneficial protective effects of BCG against disseminated disease in childhood. Recombinant poxviruses are powerful boosting agents, for both CD4+ and CD8+ T cells. Here we review the preclinical data from a BCG prime-recombinant modified vaccinia virus Ankara expressing antigen 85A (MVA85A) boost strategy. MVA85A is now in clinical trials in the UK and Africa and the design of these trials, including the ethical and regulatory issues are discussed.

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Available from: Helen A Fletcher
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    • "It is a recombinant strain of Modified Vaccinia virus Ankara expressing the Mtb antigen 85A (Ag85A), designed to enhance response induced by BCG [21]. The live viral vector cannot replicate in human. "
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    ABSTRACT: one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued. a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and websites. 100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed. Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050.
    Full-text · Article · Jan 2014 · BMC Infectious Diseases
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    • "Some studies have shown that boosting induces better protection against TB in cattle [37], [38], [39], [13], [40], [41], our results agree with those reports, the boosted group of animals had the highest concentration of IFN-g, the lowest number of lesions at slaughter and a the lowest number of bacilli in affected tissue. "
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    ABSTRACT: "Test-and-slaughter" has been successful in industrialized countries to control and eradicate tuberculosis from cattle; however, this strategy is too expensive for developing nations, where the prevalence is especially high. Vaccination with the Calmette-Guérin (BCG) strain has been shown to protect against the development of lesions in vaccinated animals: mouse, cattle and wildlife species. In this study, the immune response and the pathology of vaccinated (BCG-prime and BCG prime-CFP-boosted) and unvaccinated (controls) calves were evaluated under experimental settings. A 10(6) CFU dose of the BCG strain was inoculated subcutaneously on the neck to two groups of ten animas each. Thirty days after vaccination, one of the vaccinated groups was boosted with an M. bovis culture filtrate protein (CFP). Three months after vaccination, the three groups of animals were challenged with 5×10(5) CFU via intranasal by aerosol with a field strain of M. bovis. The immune response was monitored throughout the study. Protection was assessed based on immune response (IFN-g release) prechallenge, presence of visible lesions in lymph nodes and lungs at slaughter, and presence of bacilli in lymph nodes and lung samples in histological analysis. Vaccinated cattle, either with the BCG alone or with BCG and boosted with CFP showed higher IFN-g response, fewer lesions, and fewer bacilli per lesion than unvaccinated controls after challenge. Animals with low levels of IFN-g postvaccine-prechallenge showed more lesions than animals with high levels. Results from this study support the argument that vaccination could be incorporated into control programs to reduce the incidence of TB in cattle in countries with high prevalence.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "Rhesus macaques were immunized with 108 PFU of MVA-Ag85A or MVA-Ag85A IMX313 at weeks 0 and 6, and the response to antigen 85A was measured by IFN-γ ELISpot 1 week after vaccination, then every 2 weeks using a single pool of 66 peptides (Figure 3A) and 7 pools of 20 peptides each (Figure 3B). The peak of the antigen 85A-specific responses was observed 1 week after each vaccination (Figure 3A and B) consistent with previous data in mice and humans [20]. At multiple timepoints, higher antigen 85A responses were observed in the group of animals vaccinated with the MVA-Ag85A IMX313 when compared to those vaccinated with MVA-Ag85A (Figure 3). "
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