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ISSN 0582-9879 Acta Biochim et Biophysica Sinica 2004, 36(4):269-276 CN 31-1300/Q

Protection of Mice with a Divalent Tuberculosis DNA Vaccine
Encoding Antigens Ag85B and MPT64

Xia TIAN, Hong CAI, and Yu-Xian ZHU*
( The National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing 100871, China)

Abstract DNA vaccine may be a promising tool for controlling tuberculosis development. However, vaccines encoding single antigens of mycobacterium did not produce protective effect as BCG did. In the present study, we evaluated the immunogenicity and protective efficacy of a divalent DNA vaccine encoding two immunodominant antigens Ag85B and MPT64 of Mycobacterium tuberculosis. We found that both humoral and Th1-type (high IFN-g, low IL-4) cellular responses obtained from the divalent DNA vaccine group were significantly higher than that conferred by BCG. RT-PCR results showed that antigens were expressed differentially in various organs in divalent DNA vaccine group. The survival rate for mice treated with the divalent DNA vaccine after challenging with high doses of virulent M. tuberculosis H37Rv was significantly higher than that of the BCG group or any of the single DNA vaccine group. Significant differences were also found between the single and divalent DNA vaccinated mice in terms of body, spleen and lung weight. Bacterial loading decreased about 2000-fold in lungs and about 100-fold in spleens of divalent DNA vaccinated mice when compared with that of the control group. We conclude that our divalent DNA vaccine may be a better choice for controlling tuberculosis disease in animals.

Key words tuberculosis; divalent DNA vaccine; immunogenicity; protection

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Received: December 8, 2003 Accepted: March 2, 2004
This work was supported by a grant from the National 863 high technology program, the Chinese Ministry of Science and Technology (grant No. 2001AA213141).
*Corresponding author: Tel, 86-10-62751193; Fax, 86-10-62754427; E-mail, zhuyx@water.pku.edu.cn