Article

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: 3.5). 01/2005; 85(1-2):47-52. DOI: 10.1016/j.tube.2004.09.015
Source: PubMed

ABSTRACT 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, Aug 31, 2015
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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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    • "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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    PLoS ONE 10/2013; 8(10):e76418. DOI:10.1371/journal.pone.0076418 · 3.23 Impact Factor
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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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    ABSTRACT: To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4(+) and CD8(+) T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability.
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