Bacterial DNA Containing Methylated CpG Motifs Retains Immunostimulatory Activity in Synergy with Modified Lipopolysaccharides

Cho, Yang Je; Ahn, Bo Young; Song, Eun Sun; Park, Shin Ae; Lee, Dong Hoon; Kim, Doo-Sik; Lee, Na Gyong

doi:10.1111/j.1348-0421.2007.tb03903.x

Cited by 4 publications

(2 citation statements)

References 40 publications

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“…Induction of antigen-specific CD8 1 T cells by CIA07, as determined by staining with HBsAg peptide-MHC I pentamers, suggests stimulation of HBsAg-specific cytotoxic T cell formation by CIA07. In previous experiments, CIA07 enhanced the secretion of IL-12 and IFN-g from human PBMC, confirming its ability to induce Th1-type cellular immune responses in humans (Cho et al, 2006(Cho et al, , 2007. These data collectively demonstrate that CIA07 induces both Th1-and Th2-type responses to recombinant HBsAg.…”

Section: Discussionsupporting

confidence: 73%

Adjuvant effect of CIA07, a combination ofEscherichia coliDNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen

Song¹,

Park²,

Kim³

et al. 2007

FEMS Immunology &Amp; Medical Microbiology

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CIA07 is an immunostimulatory agent composed of bacterial DNA fragments and modified lipopolysaccharide, which has antitumor activity against bladder cancer in mice. In this study, the adjuvant activity of CIA07 was evaluated using hepatitis B virus surface antigen (HBsAg) as the immunogen. Mice were immunized intramuscularly three times at 1-week intervals with HBsAg alone or in combination with alum, bacterial DNA fragments, modified lipopolysaccharide, CIA07 or CpG1826, and immune responses were assessed. At 1 week after the final injection, the HBsAg-specific total serum IgG antibody titer in CIA07-treated mice was 14 times higher than that in animals administered antigen alone, six times higher than in mice given alum or bacterial DNA fragments and twice as high as those treated with modified lipopolysaccharide or CpG1826, and remained maximal until 8 weeks postimmunization. Animals receiving antigen alone or plus alum displayed barely detectable HBsAg-specific serum IgG2a antibody responses. However, coadministration of CIA07 with antigen led to markedly enhanced serum IgG2a antibody titer and IFN-gamma(+) production in splenocytes, indicating that CIA07 effectively induces Th1-type immune responses. In addition, the number of HBsAg-specific CD8(+) T cells in peripheral blood mononuclear cells was elevated in CIA07-treated mice. These data clearly demonstrate that CIA07 is able to induce both cellular and humoral immune responses to HBsAg, and confirm its potential as an adjuvant in therapeutic vaccines for hepatitis B virus infections.

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Section: Discussionsupporting

confidence: 73%

Adjuvant effect of CIA07, a combination ofEscherichia coliDNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen

Song¹,

Park²,

Kim³

et al. 2007

FEMS Immunology &Amp; Medical Microbiology

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“…We combined this fragment with a short carbohydrate chain-expressing LPS that had been alkalinehydrolyzed to remove lipid A. The resulting mixture, designated CIA07, was more immunostimulatory than either substance alone, and exhibited significantly higher antitumor activity in a mouse bladder cancer model than Bacillus Calmette-Guerin (BCG), which is in current clinical use as immunotherapy for bladder cancer treatment (13,14). Moreover, CIA07 was observed to induce significantly low TNF-α secretion in human whole blood assays, and did not cause apparent adverse reactions in animals, suggesting potential as a novel immunomodulatory agent.…”

mentioning

confidence: 99%

Immune Responses of Mice to Influenza Subunit Vaccine in Combination with CIA07 as an Adjuvant

Park

Song

Cho³

et al. 2007

Microbiology and Immunology

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CIA07 is an immunostimulatory agent composed of E. coli DNA fragments and modified LPS lacking the lipid A moiety. In this study, we investigated whether CIA07 promotes immune responses as an adjuvant to the influenza subunit vaccine. Balb/c mice were immunized intramuscularly once or twice at a 4-week interval with the trivalent influenza subunit vaccine antigen alone or in combination with CIA07 as adjuvant. Antigen-specific serum antibody titers and hemagglutination-inhibition (HI) antibody titers were assessed. At 4 weeks after each immunization, the antigen-specific total serum IgG antibody titer in mice receiving CIA07 was 2 to 3 times higher than that in animals administered antigen alone (P<0.05). The CIA07-treated group additionally displayed higher HI antibody titers against each of the 3 vaccine strains, compared to the antigen group. Animals receiving antigen alone displayed barely detectable antigen-specific serum IgG2a antibody titers. In contrast, coadministration of CIA07 with antigen led to significantly enhanced IgG2a antibody responses, suggesting that CIA07 stimulates a Th1-type immune response. Moreover, the CIA07-treated group displayed a marked increase in the number of interferon ␥-producing CD8؉ T cells in splenocytes. These data collectively demonstrate that CIA07 has the ability to induce both Th1-type cellular and Th2-type humoral immune responses to the influenza subunit vaccine, and support its potential as an effective adjuvant to the influenza vaccine.

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Enhancement of the immune responses of mice to Bacillus anthracis protective antigen by CIA07 combined with alum

et al. 2008

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Anthrax is an acute zoonotic disease caused by infection with Bacillus anthracis. B. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. In this study, we investigated the adjuvant activity of CIA07 to anthrax protective antigen (PA). A/J mice were immunized intraperitoneally once, or twice with a 4-week interval, with recombinant PA alone or combined with alum, CpG1826, or CIA07 as adjuvant, and serum anti-PA IgG antibody responses were measured 4 weeks after each immunization. All three adjuvants significantly enhanced anti-PA IgG antibody titer 4 weeks after the priming and boosting immunizations, and alum gave the highest titer. In order to evaluate the adjuvant activity of CIA07 in the presence of alum, Balb/c mice were immunized 3 times at 1-week intervals with PA in combination with alum, CIA07 or alum plus CIA07, and the immune responses were assessed 2 weeks after the third immunization. The serum anti-PA IgG antibody titer of the CIA07-treated group was 14-fold higher than the group given PA alone, and the coadministration of CIA07 with alum further increased the titer 3.5-fold (P < 0.05). The toxin neutralizing activity of the sera from the mice given the combination of CIA07 and alum was 109-times higher than the animals given PA alone. The mice given CIA07 plus alum also showed a marked increase in the number of IFN-gamma-, IL-2-, and IL-4-producing CD4(+) T cells among their splenocytes. These data suggest the potential of CIA07 in combination with alum as an adjuvant for the development of a potent anthrax vaccine.

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Bacterial DNA Containing Methylated CpG Motifs Retains Immunostimulatory Activity in Synergy with Modified Lipopolysaccharides

Cited by 4 publications

References 40 publications

Adjuvant effect of CIA07, a combination ofEscherichia coliDNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen

Adjuvant effect of CIA07, a combination ofEscherichia coliDNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen

Immune Responses of Mice to Influenza Subunit Vaccine in Combination with CIA07 as an Adjuvant

Enhancement of the immune responses of mice to Bacillus anthracis protective antigen by CIA07 combined with alum

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