Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine.
Brucella abortus S19 is the vaccine most frequently used against bovine brucellosis. Although it induces good protection levels, it cannot be administered to pregnant cattle, revaccination is not advised due to interference in the discrimination between infected and vaccinated animals during immune-screening procedures, and the vaccine is virulent for humans. Due to these reasons, there is a continuous search for new bovine vaccine candidates that may confer protection levels comparable to those conferred by S19 but without its disadvantages. A previous study characterized the phenotype associated with the phosphoglucomutase (pgm) gene disruption in Brucella abortus S2308, as well as the possible role for the smooth lipopolysaccharide (LPS) in virulence and intracellular multiplication in HeLa cells (J. E. Ugalde, C. Czibener, M. F. Feldman, and R. A. Ugalde, Infect. Immun. 68:5716-5723, 2000). In this report, we analyze the protection, proliferative response, and cytokine production induced in BALB/c mice by a deltapgm deletion strain. We show that this strain synthesizes O antigen with a size of approximately 45 kDa but is rough. This is due to the fact that the deltapgm strain is unable to assemble the O side chain in the complete LPS. Vaccination with the deltapgm strain induced protection levels comparable to those induced by S19 and generated a proliferative splenocyte response and a cytokine profile typical of a Th1 response. On the other hand, we were unable to detect a specific anti-O-antigen antibody response by using the fluorescence polarization assay. In view of these results, the possibility that the deltapgm mutant could be used as a vaccination strain is discussed.
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín, Consejo Nacional de Investigaciones Científicas, Buenos Aires, Argentina.
Juan Esteban
JE
Ugalde
Diego José
DJ
Comerci
M Susana
MS
Leguizamón
Rodolfo Augusto
RA
Ugalde
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D019081:O Antigens / Q000096:biosynthesis / Q000276:immunology; D010641:Phenotype; D010733:Phosphoglucomutase / Q000235:genetics*; D014774:Virulence
D000907:Antibodies, Bacterial; D002004:Brucella Vaccine; D019081:O Antigens; D015847:Interleukin-4; D007371:Interferon-gamma; D010733:Phosphoglucomutase