RECOMBINANT BCG STRAINS WITH ENHANCED ABILITY TO INHIBIT INTRACELLULAR MYCOBACTERIAL GROWTH

摘要

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.

主权项

1. 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.