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 vaccines.
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]