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Vaccination of Guinea Pigs with DNA Encoding the Mycobacterial Antigen MPB83 Influences Pulmonary Pathology but Not Hematogenous Spread following Aerogenic Infection with Mycobacterium bovis

Mark A. Chambers,^1* Ann Williams,² Graham Hatch,² Dolores Gavier-Widén,^3, Graham Hall,⁴ Kris Huygen,⁵ Douglas Lowrie,⁶ Philip D. Marsh,² and R. Glyn Hewinson¹

TB Research Group, Department of Bacterial Diseases,¹ Department of Pathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey, KT15 3NB,,³ Research Division,² Pathology, CAMR, Salisbury, SP4 0JG,,⁴ NIMR, Mill Hill, London, United Kingdom,⁶ Department of Virology, Pasteur Institute, B-1180 Brussels, Belgium⁵

Received 13 September 2001/ Returned for modification 24 October 2001/ Accepted 17 December 2001

Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistent Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a tuberculin test and slaughter control program. The main aim of such a vaccination strategy would be to reduce transmission of infection by reducing the lung pathology caused by infection and preventing seeding of the organism to organs from which M. bovis could be excreted. Recent reports of successful DNA vaccination against Mycobacterium tuberculosis in small-animal models have suggested that DNA vaccines act by reducing lung pathology without sensitizing animals to tuberculin testing. We therefore evaluated the ability of vaccines consisting of DNA encoding the mycobacterial antigens MPB83 and 85A to reduce lung pathology and prevent hematogenous spread in guinea pigs challenged with a low dose of aerosolized M. bovis. Vaccination with MPB83 DNA reduced the severity of pulmonary lesions, as assessed by histopathology, and resembled M. bovis BCG vaccination in this respect. However, unlike BCG vaccination, MPB83 DNA vaccination did not protect challenged guinea pigs from hematogenous spread of organisms to the spleen. In contrast, vaccination with antigen 85A DNA, a promising DNA vaccine for human tuberculosis, had no measurable protective effect against infection with M. bovis.

Editor: S. H. E. Kaufmann

Present address: Division of Wildlife, SVA (National Veterinary Institute), S-750 07 Uppsala, Sweden.

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