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

Abstract:

: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.

journal_name

Vaccine

journal_title

Vaccine

authors

Yu DH,Li M,Hu XD,Cai H

doi

10.1016/j.vaccine.2007.06.061

subject

Has Abstract

pub_date

2007-09-17 00:00:00

pages

6744-54

issue

37-38

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(07)00763-3

journal_volume

25

pub_type

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