• IMMUNE NETWORK
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• v.7 no.4
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• pp.186-196
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• 2007

Background: Although IL-12 has been widely accepted to playa central role in the control of pathogen infection, the use of recombinant IL-12 (rIL-12) as a vaccine adjuvant has been known to be ineffective because of its rapid clearance in the body. Methods: To investigate the effect of sustained release of IL-12 in vivo in the peptide and protein vaccination models, rIL-12 was encapsulated into poly ($A_{DL}$-lactic-co-glycolic acid) (PLGA). Results: We found that codelivery of IL-12-encapsulated microspheres (IL-12EM) could dramatically increase not only antibody responses, but also antigen-specific $CD4^+\;and\;CD8^+$ T cell responses. Enhanced immune responses were shown to be correlated with protective immunity against influenza and respiratory syncytial virus (RSV) virus challenge. Interestingly, the enhancement of $CD8^+$ T cell response was not detectable when $CD4^+$ T cell knockout mice were subjected to vaccination, indicating that the enhancement of the $CD8^+$ T cell response by IL-12EM is dependent on $CD4^+$ T cell "help". Conclusion: Thus, IL-12EM could be applied as an adjuvant of protein and peptide vaccines to enhance protective immunity against virus infection.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.210-218
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• 2013

Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-${\gamma}$ secretion. Moreover, increased mRNA expression of IFN-${\gamma}$, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.

• Clinical and Experimental Pediatrics
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• v.51 no.7
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• pp.696-703
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• 2008

Korea is now classified as an area of intermediate endemicity for hepatitis B virus (HBV), due to the implementation of universal HBV vaccination and national preventive programs for HBV infection. A national program of HBV vaccination was launched in Korea in 1988 for school-going children and was listed on a vaccination guideline in 1991. In 1995, universal vaccination for newborn infants was started for the prevention of perinatal HBV transmission. The prevalence of HBsAg among Korean middle school students has shown marked decreased from 3.2% in the late 1990s to 0.44% in 2007. HBsAg positivity in preschool children was 0.9% in 1995, decreased to 0.2% in 2007 by national prevention program of hepatitis B vertical transmission, launched in 2002. Vaccine failure rate of HBV immunoprophylaxis is 4.2% by this program. The infected children should be monitored per 6-12 months interval. Lamivudine and interferon are approved therapies for children with chronic hepatitis B in immune-clearance phase in Korea.

• Genomics & Informatics
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• v.7 no.4
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• pp.187-194
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• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

• Microbiology and Biotechnology Letters
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• v.43 no.3
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• pp.267-274
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• 2015

Biopharmaceuticals and the cell substrates used for their manufacture are currently tested for porcine adventitious viruses due to the widespread use of porcine trypsin in cell culture. Porcine transmissible gastroenteritis virus (PTGV) is one of the major adventitious porcine viruses causing contaminated during the manufacture of biopharmaceuticals. Therefore, rapid and sensitive detection of PTGV is essential in ensuring the safety of biopharmaceuticals. A TaqMan probe real-time RT-PCR method was developed for the quantitative detection of PTGV contamination in cell substrates, raw materials, manufacturing processes, and final products, as well as PTGV clearance validation. Specific primers for the amplification of PTGV RNA were selected, and PTGV RNA was quantified by use of a specific TaqMan probe. Specificity, limit of detection (LOD), and robustness of the method was validated according to international guidelines on the validation of nucleic acid amplification tests. The sensitivity of the assay was calculated to be 1.10 × 10⁰ TCID₅₀/ml. The real-time RT-PCR method was validated to be reproducible, very specific to PTGV, and robust. The established real-time RT-PCR assay was successfully applied to the validation of Chinese Hamster Ovary (CHO)-K1 cells artificially infected with PTGV.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3381-3384
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• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• Korean Journal of Microbiology
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• v.44 no.3
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• pp.228-236
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• 2008

Validation of viral safety is essential in ensuring the safety of mammalian cell culture-derived biopharmaceuticals, because numerous adventitious viruses have been contaminated during the manufacture of the products. Mammalian cells are highly susceptible to Reovirus type 3 (Reo-3), and there are several reports of Reo-3 contamination during the manufacture of biopharmaceuticals. In order to establish the validation system for the Reo-3 safety, a real-time RT-PCR method was developed for quantitative detection of Reo-3 in cell lines, raw materials, manufacturing processes, and final products as well as Reo-3 clearance validation. Specific primers for amplification of Reo-3 RNA was selected, and Reo-3 RNA was quantified by use of SYBR Green I. The sensitivity of the assay was calculated to be $3.2{\times}10^0\;TCID_{50}/ml$. The real-time RT-PCR method was proven to be reproducible and very specific to Reo-3. The established real-time RT-PCR assay was successfully applied to the validation of Chinese hamster ovary (CHO) cell artificially infected with Reo-3. Reo-3 RNA could be quantified in CHO cell as well as culture supernatant. When the real-time RT-PCR assay was applied to the validation of virus removal during a virus filtration process, the result was similar to that of virus infectivity assay. Therefore, it was concluded that this rapid, specific, sensitive, and robust assay could replace infectivity assay for detection and clearance validation of Reo-3.

• Biotechnology and Bioprocess Engineering:BBE
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• v.4 no.1
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• pp.63-65
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• 1999

Although many pharmaceutically useful proteins are produced in E. coli expression system, it is very are rare for the system to be used in the production of diagnostic antigen due to a major problem, i.e., false-positive reaction of e. coli host-derived proteins contaminating purified diagnostic antigen with human sera. The N (nucleocapsid) protein of Seoul virus causing haemorrhagic fever with renal syndrome (HFRS) was produced in E. coli BL21 (DE3), and used for the detection of N protein-specific antibodies in human sera. Using the N protein as a diagnostic antigen of HFRS, the false-positive reaction was cleared by merely mixing the test sera with the extract of E. coli host strain not harboring expression plasmid.

• Journal of fish pathology
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• v.27 no.2
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• pp.85-89
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• 2014

Water temperature is a key environmental factor controlling the epizootics of viral diseases in fish. High water temperature is associated with the rapid spread of rock bream iridovirus (RBIV) disease and with high mortality of RBIV infected fish. Although protection of fish against iridoviral disease by active immunization has been reported, little information is available concerning whether fish survived from an epizootic of iridoviral disease can naturally acquire resistance against the viral disease. In the present study, we have demonstrated that juvenile rock bream, which survived from a natural epizootic of RBIV, acquired resistance against recurrence or reinfection of RBIV, and this resistance was established during the subsequent low water temperature period. Furthermore, the possible involvement of the adaptive humoral immune response in the resistance of the juvenile rock bream was suggested by in vivo neutralization experiment.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.194-204
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• 2020

The detrimental impact of air pollution as a result of frequent exposure to fine particles posed a global public health risk mainly to the pulmonary disorders in pediatric and geriatric population. Here, we reviewed the current literature regarding the role of ginseng and/or its components as antimicrobials, especially against pathogens that cause respiratory infections in animal and in vitro models. Some of the possible mechanisms for ginseng-mediated viral inhibition suggested are improvements in systemic and mucosa-specific antibody responses, serum hemagglutinin inhibition, lymphocyte proliferation, cell survival rate, and viral clearance in the lungs. In addition, ginseng reduces the expression levels of proinflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-8) and chemokines produced by airway epithelial cells and macrophages, thus preventing weight loss. In case of bacterial infections, ginseng acts by alleviating inflammatory cytokine production, increasing survival rates, and activating phagocytes and natural killer cells. In addition, ginseng inhibits biofilm formation and induces the dispersion and dissolution of mature biofilms. Most clinical trials revealed that ginseng, at various dosages, is a safe and effective method of seasonal prophylaxis, relieving the symptoms and reducing the risk and duration of colds and flu. Taken together, these findings support the efficacy of ginseng as a therapeutic and prophylactic agent for respiratory infections.