A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector.
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.
The National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing 100871, China.
Da-Hai
DH
Yu
Min
M
Li
Xi-Dan
XD
Hu
Hong
H
Cai
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002003:Brucella abortus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D007114:Immunization; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D019444:Vaccines, DNA; D054353:Perforin; D018664:Interleukin-12; D009569:Nitric Oxide