Rationale: Novel tuberculosis (TB) vaccines should be safe and effective in populations infected with Mycobacterium tuberculosis (M.tb) and/or HIV for effective TB control.
Objective: To determine the safety and immunogenicity of MVA85A, a novel TB vaccine, among M.tb and/or HIV-infected persons in a setting where TB and HIV are endemic.
Methods: An open-label, phase IIa trial was conducted in 48 adults with M.tb and/or HIV infection. Safety and immunogenicity were analyzed up to 52 weeks after intradermal vaccination with 5 x 107 plaque forming units of MVA85A. Specific T cell responses were characterized by IFN-γ ELISpot and whole blood intracellular cytokine staining assays.
Measurements and Main Results: MVA85A was well tolerated and no vaccine-related serious adverse events were recorded. MVA85A induced robust and durable response of mostly polyfunctional CD4 T cells, co-expressing IFN-γ, TNF-α and IL-2. Magnitudes of pre- and post-vaccination T cell responses were lower in HIV-infected, compared with HIV-uninfected, vaccinees. No significant effect of ART on immunogenicity of MVA85A was observed.
Conclusions: MVA85A was safe and immunogenic in persons with HIV and/or M.tb infection. These results support further evaluation of safety and efficacy of this vaccine for prevention of TB in these target populations.
Scriba, T.J.; Tameris, M.; Smit, E.; van der Merwe, L.; Hughes, E.J.; Kadira, B.; Mauff, K.; Moyo, S.; Brittain, N.; Lawrie, A.; Mulenga, H.; de Kock, M.; Makhethe, L.; van Rensburg, E.J.; Gelderbloem, S.; Veldsman, A.; Hatherill, M.; Geldenhuys, H.; Hill, A.V.; Hawkridge, A.; Hussey, G.D.; Hanekom, W.A.; McShane, H.; Mahomed, H. A Phase IIa Trial of the New Tuberculosis Vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected Adults. American Journal of Respiratory and Critical Care Medicine (2012) 185 (7) 769-778. [DOI: 10.1164/rccm.201108-1548OC]