23:T4d8,Adjuvant CIA09, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based cationic liposomes and the toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS), has been shown to enhance antibody and cellular immune responses to varicella-zoster virus (VZV) glycoprotein E (gE), recombinant tuberculosis vaccine antigen, and inactivated Japanese encephalitis vaccine. In this study, we investigated its modes of action using VZV gE as a model antigen. Liposomes adsorbed gE and cooperatively with dLOS promoted endocytosis-mediated cellular uptake of gE by mouse dendritic cells in vitro. CIA09 increased the stability and cellular uptake of the antigen at the muscle site of injection, and induced immune cell recruitment and cytokine and chemokine production, which led to efficient antigen delivery to draining lymph nodes. Mouse bone marrow-derived dendritic cells, pulsed with CIA09-adjuvanted gE, efficiently presented gE to antigen-specific T cells, inducing Th1-type biased immunity, as shown by high IFN-γ production. The data indicate that liposomes and dLOS cooperate in the adjuvant activity of CIA09 by promoting antigen uptake and delivery to lymph nodes as well as antigen presentation to T cells.24:T529,Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Bacillus Calmette-Guérin (BCG) vaccine is the only TB vaccine currently available, but it is not sufficiently effective in preventing active pulmonary TB or adult infection. With the purpose of developing an improved vaccine against TB that can overcome the limitations of the current BCG vaccine, we investigated whether adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS) are capable of enhancing the immunogenicity and protective efficacy of TB subunit vaccine. The results revealed that dLOS/dimethyl dioctadecyl ammonium bromide (DDA) adjuvant formulation significantly increased both humoral and Th1-type cellular responses to TB subunit vaccine that are composed of three antigens, Ag85A, ESAT-6, and HspX. The adjuvanted TB vaccine also effectively induced Th1-type response in a BCG-primed mouse model, suggesting a potential as a booster vaccine. Finally, dLOS/DDA-adjuvanted TB vaccine showed protective efficacy against M. tuberculosis infection in vitro and in vivo. These data indicate that dLOS/DDA adjuvant enhances the Th1-type immunity and protective efficacy of TB subunit vaccine suggesting that it would be a promising adjuvant candidate for development of a booster vaccine.25:T4e4,Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response. Mice immunized with the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles, and both CD4⁺ and CD8⁺ T cell responses were induced. Immunization of mice with the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon lethal challenges with influenza virus, and no excessive inflammatory responses were observed in the lung tissues of the immunized mice after viral infection. These data suggest that the dLOS-based adjuvant system CIA06 can be used to promote the immune responses to influenza vaccine or to spare antigen dose without causing harmful inflammatory responses.

#	Concept	H-Index	Publications	Citations
1	Medicine	4	4	92
2	Immunology	4	4	92
3	Microbiology	2	2	37
4	Biochemistry	1	1	22
5	Cell Biology	1	1	33

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