One strategy for improving anti-tuberculosis (TB) vaccination involves
the use of recombinant Bacillus Calmette Guérin (rBCG) overexpressing
protective TB antigens. rBCG30, overexpressing the Mycobacterium
tuberculosis secreted antigen, Ag85b, was the first rBCG shown to induce
significantly greater TB protection in animals than parental BCG.
The authors report the first phase I, double-blind trial of rBCG30 in 35
adults randomized to receive rBCG30 or parental Tice BCG intradermally.
Clinical reactogenicity was assessed and state-of-the-art immunological
assays used to study Ag85b-specific immune responses induced by both
Similar clinical reactogenicity occurred with both vaccines. rBCG30
induced significantly increased Ag85b-specific T cell
lymphoproliferation, IFN-γ secretion, IFN-γ ELISPOT responses, and
direct ex vivo intracellular IFN-γ responses. Additional flow cytometric
studies measuring CFSE dilution and intracellular cytokine production
demonstrated that rBCG30 significantly enhanced Ag85b-specific CD4+ and
CD8+ T cells capable of concurrent expansion and effector function. More
importantly, rBCG30 significantly increased Ag85b-specific T cells
capable of inhibiting intracellular mycobacteria.
These results provide proof-of-principal that rBCG can safely enhance
human TB immunity, and support further development of rBCG
overexpressing Ag85b for TB vaccination.
Hoft, D.F.; Blazevic, A.; Abate, G.; Hanekom, W.A.; Kaplan, G.; Soler, J.H.; Weichold, F.; Geiter, L.; Sadoff, J.C.; Horwitz, M.A. A New Recombinant Bacille Calmette&#8208;Guérin Vaccine Safely Induces Significantly Enhanced Tuberculosis&#8208;Specific Immunity in Human Volunteers. Journal of Infectious Diseases (2008) 198 (10) 1491-1501. [DOI: 10.1086/592450]
A New Recombinant BCG Vaccine Safely Induces Significantly Enhanced TB-specific Immunity in Human Volunteers.