Protection against tuberculosis by a plasmid DNA vaccine.
Past attempts to use fractions of mycobacteria as an alternative to BCG have given disappointing results. The availability of cloned genes and suitable vectors has now opened a new avenue in which individual mycobacterial protein antigens are synthesised within transfected mammalian cells. In an ex vivo transfection approach with a retroviral vector we found that even a single antigen (hsp65) could evoke strong protection when expressed as a transgene and that expression of protection was largely a function of antigen specific cytotoxic T cells. We now find that intramuscular injection of plasmid DNA expressing the antigen from either a viral or a murine promoter can also give protection equivalent to Bacillus Calmette-Guérin (BCG). Plasmids expressing some other mycobacterial antigens, hsp70, 36 kDa and 6 kDa, are also effective, suggesting that this approach may lead to a new vaccine.
Lowrie
D B
DB
NIMR, London, UK.
Silva
C L
CL
Colston
M J
MJ
Ragno
S
S
Tascon
R E
RE
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009166:Mycobacterium leprae / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma; D018833:Chaperonins