Identification of antigens that provide protective immunity via prophylactic and therapeutic vaccination against Mycobacterium tuberculosis is critical for the development of subunit vaccines for tuberculosis (TB). In this study, we performed a head-to-head comparison of seven well-known TB antigens delivered by DNA vaccine, and evaluated their respective immunogenicities and protective efficacies in pre-and post-exposure mouse models. All TB antigens were designed as a chimeric fusion with Flt3-L to enhance antigen-specific T-cell immunity upon vaccination. Prophylactic vaccination with the Flt3L (F)-Mtb32 DNA vaccine elicited significant protection in both the spleen and lungs against M. tuberculosis challenge, comparable to the Bacillus Calmette-Guerin vaccine. F-Ag85A and F-Mtb32 DNA vaccines, in combination with chemotherapy, reduced the bacterial burden to undetectable levels in the lungs of all mice infected with M. tuberculosis. These data collectively indicate that the F-Mtb32 DNA vaccine confers the most efficient protective immunity that suppresses bacterial growth in the active or latent status of M. tuberculosis.
Bibliographical noteFunding Information:
We thank Sang-Chun Lee, Kwan Seok Lee, Bok Chae Cho and Young Jae Choi for devoted animal care, and Ji-yeung Lee for the technical assistance. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (20100002131) and by a grant from the Brain Korea 21 Project for Medical Sciences at Yonsei University (20100002132).
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology