A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector

作者：Yu Da Hai; Li Min; Hu Xi Dan; Cai Hong^*

来源：Vaccine, 2007, 25(37-38): 6744-6754.

DOI：10.1016/j.vaccine.2007.06.061

• mycobacterium tuberculosis
• brucella abortus
• combined DNA vaccine
• IL-12 adjuvant
• th 1 immune responses
• protective immunity

We examined the immunogenicity and protective efficacy of a combined DNA vaccine that included six genes encoding immunodominant antigens from Mycobacterium tuberculosis and Brucella abortus. The IL-12 adjuvant system was used for immunization in combination with the combined DNA vaccine (DNA-IL-12(+)). Mice immunized with DNA-IL-12(+) had significantly reduced CFU counts for M. tuberculosis and B. abortus in lung and spleen, respectively (P < 0.001), and DNA-IL-12(+) elicited better protection than the combined DNA vaccine alone (DNA-IL- 12(-)) or with the positive control groups after challenge with a virulent M. tuberculosis strain and B. abortus 2308 infection. The DNA-IL- 12(+) group had stronger antigen-specific IFN-gamma ELISPOT activities and higher levels of antigen-specific CD4(+) and CD8(+) T cell responses than either the DNA-IL-12(-) or positive control groups. Likewise, antigen-specific IgG titers were also much higher than in other immunized groups. Moreover, DNA-IL-12(+) gave a stronger IgG2a-skewed response than did DNA-IL-12(-). In addition, its mean concentrations of IFN-gamma and IL-2 were about 2.5- to 4.5-fold higher than those observed in the DNA-IL-12(-)-treated Mice, and were significantly higher than control groups (P < 0.01 or P < 0.001), whereas IL-4 and IL-10 secretion were lower. These results suggest that IL-12 acts as an adjuvant to enhance protective immunity against M. tuberculosis and B. abortus through the induction of stronger Th1-associated immune responses. This is the first report to show that a single combined DNA vaccine protects animals against two infectious diseases.

• 出版日期2007-9-17
• 单位北京大学; 新疆畜牧科学院