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Wui, Seo Ri,Kim, Kwang Sung,Ryu, Ji In,Ko, Ara,Do, Hien Thi Thu,Lee, Yeon Jung,Kim, Hark Jun,Lim, Soo Jeong,Park, Shin Ae,Cho, Yang Je,Kim, Chang-Gyeom,Lee, Na Gyong Elsevier 2019 Vaccine Vol.37 No.15
<P><B>Abstract</B></P> <P>Varicella zoster virus (VZV) is a neurotropic and lymphotropic alpha herpesvirus that causes varicella and herpes zoster (HZ). At a primary infection, VZV causes varicella in young children. Reactivation of latent VZV in sensory ganglia causes painful HZ in elderly people, occasionally leading to a serious complication, postherpetic neuralgia (PHN). A live attenuated VZV vaccine, the first vaccine licensed for the prevention of HZ and PHN is not very effective, while a recombinant subunit vaccine provides higher and longer protection against HZ. In the present study, we developed a new adjuvant system CIA09A, which is composed of cationic liposomes, the Toll-like receptor 4 (TLR4) agonist de-<I>O</I>-acylated lipooligosaccharide, and <I>Quillaja</I> saponin fraction QS-21. We then determined its adjuvant activity for recombinant VZV glycoprotein E (gE) in mice. Co-lyophilization of the liposomal adjuvant formulation with gE did not abolish the immune-stimulating activity. In fact, the CIA09A-adjuvanted gE vaccine was highly effective in eliciting both humoral and cellular immune responses to the recombinant gE protein and VZV in a VZV-primed mouse model. Furthermore, the frequency of gE-specific polyfunctional CD4<SUP>+</SUP> T cells expressing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2 was significantly increased in mice immunized with the adjuvanted vaccine. These data indicate that co-lyophilization of protein antigens with CIA09A enables development of a liposome-adjuvanted vaccine in a single vial to induce strong cell-mediated immunity required for vaccine efficacy. Thus, the CIA09A-adjuvanted gE vaccine warrants further development as a new prophylactic vaccine against HZ.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We determined the adjuvanticity of CIA09A (cationic liposomes with a TLR4 ligand and QS-21) for VZV gE. </LI> <LI> Co-lyophilization of CIA09A with gE did not abolish the immune-stimulating activity for VZV gE. </LI> <LI> The CIA09A-adjuvanted gE vaccine effectively elicited humoral and CMI responses to gE and VZV. </LI> <LI> The adjuvanted vaccine induced gE-specific CD4<SUP>+</SUP> T cells expressing IFN-γ, TNF-α, and IL-2. </LI> <LI> Co-lyophilization of VZV gE with CIA09A enables manufacture of a subunit vaccine in a single vial. </LI> </UL> </P>
( Ara Ko ),( Seo Ri Wui ),( Ji In Ryu ),( Yeon Jeong Lee ),( Do Thi Thu Hien ),( Inmoo Rhee ),( Sung Jae Shin ),( Shin Ae Park ),( Kwang Sung Kim ),( Yang Je Cho ),( Na Gyong Lee ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.1
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Bacillus Calmette-Guerin (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 vaccines. The results revealed that the 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 the Th1-type response in a BCG-primed mouse model, suggesting a potential as a booster vaccine. Finally, the dLOS/DDA-adjuvanted TB vaccine showed protective efficacy against M. tuberculosis infection in vitro and in vivo. These data indicate that the dLOS/DDA adjuvant enhances the Th1-type immunity and protective efficacy of the TB subunit vaccine, suggesting that it would be a promising adjuvant candidate for the development of a booster vaccine.
( Ji In Ryu ),( Seo Ri Wui ),( Ara Ko ),( Hien Thi Thu Do ),( Yeon Jeong Lee ),( Hark Jun Kim ),( Inmoo Rhee ),( Shin Ae Park ),( Kwang Sung Kim ),( Yang Je Cho ),( Na Gyong Lee ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.8
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that commonly causes fatal infections in cystic fibrosis and burn patients as well as in patients who are hospitalized or have impaired immune systems. P. aeruginosa infections are difficult to treat owing to the high resistance of the pathogen to conventional antibiotics. Despite several efforts, no effective prophylactic vaccines against P. aeruginosa are currently available. In this study, we investigated the activity of the CIA06 adjuvant system, which is composed of alum and de-Oacylated lipooligosaccharide, on a P. aeruginosa outer membrane protein (OMP) antigen vaccine in mice. The results indicated that CIA06 significantly increased the antigen-specific IgG titers and opsonophagocytic activity of immune sera against P. aeruginosa. In addition, the antibodies induced by the CIA06-adjuvanted vaccine exhibited higher cross-reactivity with heterologous P. aeruginosa strains. Finally, mice immunized with the CIA06-adjuvanted vaccine were effectively protected from lethal P. aeruginosa challenge. Based on these data, we suggest that the CIA06 adjuvant system might be used to promote the immunogenicity and protective efficacy of the P. aeruginosa OMP vaccine.
Ryu, Ji In,Park, Shin Ae,Wui, Seo Ri,Ko, Ara,Han, Ji Eun,Choi, Jung Ah,Song, Man Ki,Kim, Kwang Sung,Cho, Yang Je,Lee, Na Gyong Hindawi Publishing Corporation 2016 BioMed research international Vol.2016 No.-
<P>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-<I>O</I>-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<SUP>+</SUP> and CD8<SUP>+</SUP> 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. </P>