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

Abstract

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.

A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice

“…We also observed that CIA05 stimulates secretion of various cytokines and chemokines from human monocytes as well as mouse bone marrow dendritic cells, and the immunostimulating activity of CIA05 was higher than that of MPL (manuscript in preparation). In our previous studies, CIA05, when used alone or in combination with bacterial DNA fragmented into optimal sizes, enhanced the immunogenicity of HBsAg and influenza virus subunit vaccine [17,29]. In addition, formulation of CIA05 plus Gardasil®, which consists of HPV L1 VLPs adjuvanted with alum, significantly increased splenic IFN-γ secretion as well as the serum antibody responses, indicating that CIA05 is able to stimulate both Th1-and Th2-type immune responses in concert with alum [18].…”

A nontoxic derivative of lipopolysaccharide increases immune responses to Gardasil® HPV vaccine in mice

“…CIA07, a mixture of CIA02 and CIA05 at a ratio of 100:1, further promoted the immune responses to HBsAg. It also elicited stronger immune responses when administered with influenza virus subunit vaccine antigen [21]. In addition, CIA07 was observed to have higher antitumor activity in a mouse bladder cancer model than Bacillus Calmette-Guerin, which is in current clinical use as immunotherapy for bladder cancer [22].…”

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

“…CIA07 exhibited significantly higher antitumor activity in a mouse bladder cancer model than BCG, which is currently used as immunotherapy for bladder cancer (Cho et al, 2006. It also showed an adjuvant activity to two viral vaccine antigens, HBsAg and influenza virus subunit vaccine Park et al, 2007). In this study, we examined the potential of CIA07 as an adjuvant in a vaccine against infection with the bacterial pathogen, B. anthracis.…”