Recombinant bcg strains with enhanced ability to inhibit intracellular mycobacterial growth
AssigneeNational Health Research Institutes
InventorHorng-Yunn DOU
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Abstract
A recombinant bacterial cell strain is disclosed. It comprises: a) a first vector comprising a fusion transgene encoding Ag85B-CFP10 fusion protein, the fusion transgene being operably linked to a promoter effective for expression of the Ag85B-CFP10 fusion protein; and b) a second vector comprising a transgene encoding interleukin-12 (IL-12), the transgene being operably linked to a promoter effective for expression of the IL-12 protein. A method of inhibiting intracellular growth of Mycobacterium in a subject is also disclosed.
Claims14
A method of enhancing an immune response against M. tuberculosis, comprising:
- immunizing a subject in need thereof with a vaccine composition comprising a recombinant Bacille Calmette-Guerin (BCG) strain, the recombinant BCG strain comprising:
- (a) a first vector comprising a fusion transgene encoding Ag85B-CFP10 fusion protein, the fusion transgene being operably linked to a promoter effective for expression of the Ag85B-CFP10 fusion protein;
- and
- (b) a second vector comprising a transgene encoding a human interleukin-12 (IL-12), the transgene being operably linked to a promoter effective for expression of the human IL-12 protein, and thereby enhancing the immune response against the M. tuberculosis in the subject,
- wherein the enhanced immune response comprises:
- (i) a higher anti-Ag85b and anti-CFP10 antibody titers at 8 and/or 12 weeks post immunization;
- (ii) more CD4+ CD44+/IFN-γ+ memory T cells in lung tissues at 6 weeks post vaccination;
- and
- (iii) greater inhibition of intracellular growth of M. tuberculosis at weeks post vaccination,
- when compared with a subject vaccinated with a recombinant BCG strain comprising the fusion transgene encoding the Ag85B-CFP10 but without the transgene encoding the IL-12.
A method of enhancing an immune response against M. tuberculosis, comprising:
- immunizing a subject in need thereof with a vaccine composition comprising a recombinant Bacille Calmette-Guerin (BCG) strain comprising:
- (a) a fusion transgene encoding Ag85B-CFP10 fusion protein, the fusion transgene being operably linked to a promoter effective for an increased expression of Ag85B and CFP10 proteins;
- and
- (b) a transgene encoding a human IL-12 protein, the transgene being operably linked to a promoter effective for expression of the human IL-12 protein, and thereby enhancing the immune response in the subject,
- wherein the enhanced immune response comprises:
- greater inhibition of intracellular growth of M. tuberculosis at 8 weeks post vaccination,
- when compared with a subject vaccinated with a recombinant BCG strain comprising the fusion transgene encoding the Ag85B-CFP10 but without the transgene encoding the IL-12.
A vaccine composition comprising a recombinant Bacille Calmette-Guerin (BCG) strain, the recombinant BCG strain comprising:
- (a) a first vector comprising a fusion transgene encoding Ag85B-CFP10 fusion protein, the fusion transgene being operably linked to a promoter effective for expression of the-Ag85B-CFP10 fusion protein;
- and
- (b) a second vector comprising a transgene encoding a human interleukin-12 (IL-12), the transgene being operably linked to a promoter effective for expression of the human IL-12 protein, and
- being capable of exhibiting a characteristics of enhancing an immune response in a human subject, the enhancing immune response comprising:
- (i) eliciting a higher anti-Ag85b and anti-CFP10 antibody titers at 8 and/or 12 weeks post immunization;
- (ii) eliciting more CD4+ CD44+/IFN-γ+ memory T cells in lung tissues at 6 weeks post vaccination;
- and
- (iii) inducing greater inhibition of intracellular growth of M. tuberculosis at 8 weeks post vaccination,
- when compared with a subject vaccinated with a recombinant BCG strain comprising the fusion transgene encoding the Ag85B-CFP10 but without the transgene encoding the IL-12.
Dependencies are inferred from the claim text.