Protective immunity elicited by rBCG vaccines.
The live attenuated Mycobacterium bovis strain Bacille Calmette-Guerin (BCG) is still widely used as a vaccine against tuberculosis and therefore offers potential advantages as a safe, live vaccine vehicle for the expression and delivery of protective recombinant antigens. As an attenuated intracellular bacterium residing in macrophages, BCG would seem to be particularly suited for eliciting cellular responses and not humoral responses. Efforts to improve the potential for recombinant BCG (rBCG) vaccines to elicit protective humoral responses were undertaken by developing vectors systems which export or secrete foreign antigens. Expression of the OspA antigen of Borrelia burgdorferi, as a chimaeric membrane-associated lipoprotein, resulted in high-titred protective humoral responses when compared to cytoplasmic or secreted expression of OspA. Expression of the PspA antigen of Streptococcus pneumoniae as a secreted or membrane-associated lipoprotein by rBCG did not result in higher-titred humoral responses in comparison to PspA expressed cytoplasmically but apparently improved the quality of protective PspA specific antibodies. Based on these pre-clinical studies, rBCG vaccines for Lyme and pneumococcal diseases are being developed for clinical trials in humans. The potential for eliciting mucosal responses to antigens delivered by rBCG was also investigated. Nasal immunization was superior at eliciting substantial lasting mucosal responses at multiple mucosal sites and also resulted in systemic responses comparable to those obtained with parenteral immunization.
PathoGenesis Corp., Seattle, WA.
C K
CK
Stover
G P
GP
Bansal
S
S
Langerman
M S
MS
Hanson
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D008074:Lipoproteins; D008193:Lyme Disease / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009092:Mucous Membrane / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001500:BCG Vaccine; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D008074:Lipoproteins; C072045:OspA protein; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C069816:phage shock protein, Bacteria