• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.787-792
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• 2002

When developing a combined DTaP-HepB vaccine, toxicity and HBsAg immunogenicity are both important considerations. Thus, for a combined DTaP-HepB vaccine with a low toxicity, the effect of the DTaP content and $Al(OH)_3$, gel concentration on the vaccine toxicity was investigated. Within the range studied, the higher the concentrations, the higher the vaccine toxicity. The importance of the tetanus toxoid content in the combined DTaP-HepB vaccine was also revealed. A higher concentration of the tetanus toxoid was found to have a negative effect on the stability of the HBsAg immunogenicity in the combined vaccine. Accordingly, considering the factors affecting toxicity and HBsAg immunogenicity, a novel DTaP-HepB vaccine (30 Lf/ml of diphtheria toxoid, 5 Lf/ml of tetanus toxoid, 10 $\mu\textrm{g}$ PN/ml of acellular pertussis, 24 $\mu\textrm{g}$/ml of HBsAg, and 500 $\mu\textrm{g}$ Al/ml of $Al(OH)_3$ gel) was developed. It has a low toxicity and a stable HBsAg immunogenicity and also satisfies the potency criteria of K-FDA for a combined DTaP vaccine.

• Journal of Microbiology and Biotechnology
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• v.13 no.3
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• pp.338-343
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• 2003

Various factors, such as the adsorption pH, adjuvant dose, and adjuvant age, which affect the adsorption degree and immunogenicity of an antigen, were investigated. In addition, the effect of pH, antigen content, and adjuvant content on immunogenicity was also studied through animal experiments. Within the ranges studied, a low pH for adsorption, freshly preformed gel, and low pH formulation for the combined DTwP-HepB vaccine were preferrable for the adsorption of the antigens. In addition, a higher DT content was found to have a positive effect on the HBsAg immunogenicity in the combined vaccine. Accordingly, considering the factors affecting the adsorption rate and immunogenicity of the antigens, a novel DTwP-HepB vaccine (40 Lf/ml of diphtheria toxoid, 15 Lf/ml of tetanus toxoid, 20 OU/ml of detoxified whole cell pertussis, $24\;\mu\textrm{g}$ of HBsAg, $24\;\mu\textrm{g}\;Al/ml\;of \;Al(OH)_3\;gel,\;776\;\mu\textrm{g}\; Al/ml\;of\;AIPO_4\;gel$, and pH 7.1) was developed, whose immunogenicity was comparable to the case of administrating, separately and simultaneously, a combined DTwP vaccine (40 Lf/ml of diphtheria toxoid, 15 Lf/ml of tetanus toxoid, 20 OU/ml of detoxified whole cell pertussis, $300\;\mu\textrm{g}\;Al/ml\;of\; AIPO_4\;gel$, and pH 7.1) and mono HepB vaccine [$Hepavax^{\circledR},\;24\;\mu\textrm{g}/ml$ of HBsAg and $500\;\mu\textrm{g}\;Al/ml\;of\;Al(OH)_3\;gel$], which satisfies the potency criteria of the K-FDA for a combined DTwP vaccine and mono HepB vaccine.

• KSBB Journal
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• v.19 no.1
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• pp.88-92
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• 2004

The immunogenicity of investigational combined vaccine, composed of the Japanese encephalis virus(JEV) and the polysaccharide capsule(Vi) of Salmonella typhi covalently bound to tetanus toxoid(TT) was evaluated in mice. The mice immunized with combined vaccine elicited higher anti-Vi Immunoglobulin G(IgG) as well as anti-JEV IgG levels than the mice immunized with Vi-TT or JEV alone. The combined vaccine produced four-fold increase in anti-Vi IgG level than Vi-TT alone. In JEV the combined vaccine was significantly more immunogenic than JEV alone and induced six-fold increase in IgG level. Adsorption of combined vaccine onto aluminium hydroxide gel also enhanced IgG level for both Vi and JEV.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.174-178
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• 1997

The immnunogenicity of the possible non-essential component of the combined vaccine (KGCC-957) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated using the Hartley guinea pigs. The KGCC-95Vl was administered to the guinea pigs subcutaneously to sensitize the animals. The guinea pigs did not induce any anaphylactic immune responses which could be detectable by the active systemic anaphylaxis (ASA), the passive systemic anaphylaxis (PSA), and the passive cutaneous anaphylaxis (PCA) tests. The KGCC-95Vl is considered not to induce any anaphylactic immune responses except the prophylatic immune effects of the vaccine.

• Korean Journal of Veterinary Service
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• v.32 no.3
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• pp.201-207
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• 2009

Porcine transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and rotaviruses are considered as the most important causative agents of diarrhea in piglets. The study established 3 method vaccination programs to prevent PEDV. A (LL)group inoculated twice vaccinations on 2-weeks-interval during the late term of pregnant sows with PEDV live vaccine. The B (LKK) group was applied that one time single PEDV live vaccine at the pre-mate followed by the TGEV PEDV combined inactivated vaccine (twice vaccination on 2-weeks interval at the third-trimester). C (KK) group was applied to sow which inoculated twice vaccination on 2-weeks-interval during the late term of pregnant sows with by the TGEV, PEDV combined inactivated vaccine. As the result of SN test on sows in the pig farm before vaccination, antibody titers was showed 9/45 (20.0%). By comparison with the serum neutralizing antibody titers against PEDV of the vaccination programs after PEDV of the vaccination, A group and B group vaccination method was higher than those of C group in sows. In the piglets up to 2 weeks of age, A group was showed antibody titers of 17/22 (81.8%) that showed 2-128, and B group was showed antibody titers of 30/37 (81.1%) that showed 2-512, and C group was showed antibody titers of 14/28 (50.0%) that showed 2-32. On the other hand, PEDV antibody titers were tested for the survey. As the results of SN test, Aujeszky's disease survey in 54 pig farms from november 2005 to august 2006, antibody titers of 47/286 (16.4%) showed above 2. Five breeding farms were antibody titers of 38/77 (49.4%), Wanggung zone farms antibody titers of 59/85 (69.4%). In pigs farms vaccinated the first of twice PEDV live vaccine, and after 6 month, the second of twice TGEV PEDV combined inactivated vaccine (LLKK, 256-1024 titer) method was higher than those of vaccinated twice the early term of pregnant, and twice the late term of pregnant sows of PEDV live vaccine (LLLL, 32 titer).

• IMMUNE NETWORK
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• v.23 no.2
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• pp.16.1-16.19
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• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1042-1048
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• 2006

Plasmid DNA vaccines encoding the hepatitis B virus (HBV) surface and hepatitis C virus (HCV) envelope antigens, respectively, were constructed, and attempt were made to find the possibility of a divalent vaccine against HBV and HCV. The expression of each plasmid in Cos-1 cells was confirmed using immunocytochemistry. To measure the induced immune response by these plasmids in vivo, female BALB/c mice were immunized intramuscularly with $100\;{\mu}g$ of either both or just one of the plasmids. Anti-HBV and HCV-specific antibodies and related cytokines were evaluated to investigate the generation of both humoral and cellular immune responses. As a result, specific anti-HBV and anti-HCV serum antibodies from mice immunized with these plasmids were observed using immunoblot. The levels of IL-2 and RANTES showing a $Th_{1}$ immune response were significantly increased, but there was no change in the level of IL-4 ($Th_{1}$ immune response) in any of the immunized groups. Compared with each plasmid DNA vaccine, the combined vaccine elicited similar immune responses in both humoral and cell-mediated immunities. These results suggest that the combined DNA vaccine can induce not only comparable immunity experimentally without antigenic interference, but also humoral and $Th_{1}$ dominant cellular immune responses. Therefore, they could serve as candidates for a simultaneous bivalent vaccine against HBV and HCV infections.

• Toxicological Research
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• v.13 no.1_2
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• pp.157-160
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• 1997

The primary skin and eye irritancy of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated. The KGCC-95VI was applied to the back skins of the New Zealand White rabbits. The rabbits were observed for 72 hours and did not exhibit erythema, eschar and edema. The eyes of the rabbits were exposed to the KGCC-95VI. The rabbits were observed for 7 days and did not exhibit any ocular findings on cornea, iris and conjuntivae. The KGCC-95VI is considered not to have the primary skin and eye toxicity in rabbits.

• IMMUNE NETWORK
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• v.9 no.1
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• pp.20-26
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• 2009

We previously reported that $IFN-{\gamma}$ producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, $IFN-{\gamma}$ production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated. Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8mg of HBV DNA vaccine during the standard lamivudine treatment (100mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined. Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: $41.8{\pm}8.3$ vs. $163.1{\pm}29.2\;pg/ml$; p<0.01 and $0.96{\pm}0.25$ vs. $3.58{\pm}0.86$; p<0.01, respectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively ($218.0{\pm}41.4$ vs. $108.1{\pm}28.6\;pg/ml$; p=0.09 and $5.35{\pm}1.38$ vs. $1.80{\pm}0.29$; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine amino-transferase (ALT) in this study, contrast to $IFN-{\alpha}$ therapy which induced peak IL-12 level following ALT flares. Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

• Journal of Veterinary Science
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• v.23 no.3
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• pp.49.1-49.13
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• 2022

Background: Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (MHP) are economically significant pathogens in the pig industry. The use of combined vaccines against PCV2 and MHP is one of the most effective ways of protecting pigs from both diseases, and it has become a part of general management. Objectives: This study evaluated the efficacy of two new bivalent vaccines of PCV2 and MHP (Myco-X and Myco-XD) in SPF pigs. Myco-X and Myco-XD are a combined vaccine of MHP with PCV2b and PCV2d, respectively. Methods: Sixteen pigs were divided into four groups: Myco-X-vaccinated challenged, Myco-XD-vaccinated challenged, unvaccinated challenged, and unvaccinated unchallenged. Two milliliters of Myco-X were administered intramuscularly, and 0.5 mL of Myco-XD was injected intradermally at 3 wk of age. The pigs were challenged with virulent PCV2d via the intramuscular and intranasal route 4 wk post-vaccination. Results: All vaccinated pigs showed effective reduction of the clinical signs, the PCV2d load in the blood and nasal swab samples, as well as lung and lymphoid tissue lesions in the challenge test. Compared to unvaccinated challenged animals, the vaccinated challenged animals showed significantly higher (p < 0.05) levels of anti-PCV2 IgG, PCV2d-specific interferon-γ (IFN-γ), and anti-MHP IgG. Conclusions: Based on clinical, microbiological, serological, and pathological assessments, this study confirmed that both combined vaccines could protect pigs against PCV2 infection caused by PCV2d. On the other hand, further research on the efficacy evaluation of these new vaccines against the MHP challenge and PCV2d/MHP co-challenge is needed.