• Tony Hawkridge, Thomas J Scriba, Sebastian Gelderbloem, Erica Smit, Michele Tameris, Sizulu Moyo, Trudie Lang, Ashley Veldsman, Mark Hatherill, Linda van der Merwe, Helen A Fletcher, Hassan Mahomed, Adrian V S Hill, Willem A Hanekom, Gregory D Hussey, and Helen McShane.
• South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, Observatory, South Africa.
• J. Infect. Dis. 2008 Aug 15;198(4):544-52.

BackgroundThe efficacy of bacille Calmette-Guérin (BCG) may be enhanced by heterologous vaccination strategies that boost the BCG-primed immune response. One leading booster vaccine, MVA85A (where "MVA" denotes "modified vaccinia virus Ankara"), has shown promising safety and immunogenicity in human trials performed in the United Kingdom. We investigated the safety and immunogenicity of MVA85A in mycobacteria-exposed--but Mycobacterium tuberculosis-uninfected--healthy adults from a region of South Africa where TB is endemic.MethodsTwenty-four adults were vaccinated with MVA85A. All subjects were monitored for 1 year for adverse events and for immunological assessment.ResultsMVA85A vaccination was well tolerated and induced potent T cell responses, as measured by interferon (IFN)-gamma enzyme-linked immunospot assay, which exceeded prevaccination responses up to 364 days after vaccination. BCG-specific CD4+ T cells boosted by MVA85A were comprised of multiple populations expressing combinations of IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and IL-17, as measured by polychromatic flow cytometry. IFN-gamma-expressing and polyfunctional IFN-gamma+TNF-gamma+IL-2+ CD4+ T cells were boosted during the peak BCG-specific response, which occurred 7 days after vaccination.ConclusionThe excellent safety profile and quantitative and qualitative immunogenicity data strongly support further trials assessing the efficacy of MVA85A as a boosting vaccine in countries where TB is endemic.Trial RegistrationClinicalTrials.gov identifier: NCT00460590.

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