Abstract
The failure of current BCG vaccine in controlling the global tuberculosis (TB) epidemic highlights an urgent need for improved TB vaccine formulations. In this study, we have investigated the effect of a novel adenoviral granulocyte macrophage-colony stimulating factor (GM-CSF) transgene-based adjuvant formulation (AdGM-CSF) on BCG vaccination in a mouse strain that is genetically weak responders to BCG vaccine. BALB/c mice were immunized subcutaneously (s.c.) with PBS, BCG, or BCG plus AdGM-CSF or control vector Addl70-3, the immunogenicity of BCG vaccine was evaluated by type 1 IFN-γ production from lymphocytes of various lymphoid tissues upon mycobacterial antigen stimulation ex vivo. While mycobacterial antigen-specific IFN-γ production was slightly enhanced by co-immunization BCG with Addl70-3 as compared to BCG immunization alone, a marked increase both in the magnitude and longevity of anti-mycobacterial type 1 immunity was observed in the local draining lymph nodes and spleens by immunization with AdGM-CSF-adjuvanted BCG. Furthermore, there was a significant increase in the number of mycobacterial antigen-specific IFN-γ releasing CD4 T cells in mice immunized with AdGM-CSF-adjuvanted BCG vaccine. Consistent with these enhanced T-cell immunity and memory responses, AdGM-CSF-adjuvanted BCG vaccine significantly improved immune protection against secondary mycobacterial challenge. Our results suggest that GM-CSF transgene-based adjuvant formulation is an effective way to improve the immunogenicity of BCG vaccine.
Original language | English |
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Pages (from-to) | 2887-2898 |
Number of pages | 12 |
Journal | Vaccine |
Volume | 20 |
Issue number | 23-24 |
DOIs | |
Publication status | Published - Jul 26 2002 |
Externally published | Yes |
Bibliographical note
Funding Information:This study was supported by funds from the Canadian Institutes of Health Research (CIHR) and the Ontario Thoracic Society. J.W. holds a CIHR-Canadian Lung Association fellowship. Z.X. holds a CIHR New Investigator Award and an Ontario Premier’s Research Excellence Award.
ASJC Scopus Subject Areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases