• Toxicological Research
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• 제13권3호
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• pp.281-291
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• 1997

The subacute toxicity 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. KGCC-95VI was subcutaneously administered into the both sexes of New Zealand White rabbits at the dosage of 0, 10. 50 and 250 ml/kg body weight (20, 100 and 500 times the expected clincal dose) once a day for 30 days. There were no deaths and clinical findings during the experiment period. In both sexes. there were no statistically significant differences between the treated and control groups in urinalysis tests, hematological tests, blood chemistry tests and pathological examinations. The KGCC-95VI is considered not to have the subacute toxicity in the rabbits.

• Journal of Veterinary Science
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• 제22권3호
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• pp.30.1-30.15
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• 2021

Background: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. Objectives: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. Methods: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. Results: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4⁺ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. Conclusions: These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.304-316
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• 2021

Vaccination is the most effective way to prevent influenza virus infections. However, conventional vaccines based on hemagglutinin (HA) have to be annually updated because the HA of influenza viruses constantly mutates. In this study, we produced a 3M2e-3HA2-NP chimeric protein as a vaccine antigen candidate using an Escherichia coli expression system. The vaccination of chimeric protein (15 ㎍) conferred complete protection against A/Puerto Rico/8/1934 (H1N1; PR8) in mice. It strongly induced influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity. To spare the dose and enhance the cross-reactivity of the chimeric, we used a complex of poly-γ-glutamic acid and alum (PGA/alum) as an adjuvant. PGA/alum-adjuvanted, low-dose chimeric protein (1 or 5 ㎍) exhibited higher cross-protective effects against influenza A viruses (PR8, CA04, and H3N2) compared with those of chimeric alone or alum-adjuvanted proteins in vaccinated mice. Moreover, the depletion of CD4+ T, CD8+ T, and NK cells reduced the survival rate and efficacy of the PGA/alum-adjuvanted chimeric protein. Collectively, the vaccination of PGA/alum-adjuvanted chimeric protein induced strong protection efficacy against homologous and heterologous influenza viruses in mice, which suggests that it may be a promising universal influenza vaccine candidate.

• 한국어병학회지
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• 제37권1호
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• pp.1-8
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• 2024

The advantages of replicon vectors of RNA viruses include a high ability to stimulate innate immunity and exponential amplification of target mRNA leading to high expression of foreign antigens. The present study aimed to construct a DNA-layered nervous necrosis virus (NNV) replicon vector system in which the capsid protein gene was replaced with a foreign antigen gene and to compare the efficiency of foreign antigen expression between the conventional DNA vaccine vector and the present replicon vector. We presented the first report of a nodavirus DNA replicon-based foreign antigen expression system. Instead of a two-vector system, we devised a one-vector system containing both an NNV RNA-dependent RNA polymerase cassette and a foreign antigen-expressing cassette. This single-vector approach circumvents the issue of low foreign protein expression associated with the low co-transfection efficiency of a two-vector system. Cells transfected with a vector harboring hammerhead ribozyme-fused RNA1 and RNA2 (with the capsid gene ORF replaced with VHSV glycoprotein ORF) exhibited significantly higher transcription of the VHSV glycoprotein gene compared to cells transfected with either a vector without hammerhead ribozyme or a conventional DNA vaccine vector expressing the VHSV glycoprotein. Furthermore, the transcription level of the VHSV glycoprotein in cells transfected with a vector harboring hammerhead ribozyme-fused RNA1 and RNA2 showed a significant increase over time. These results suggest that NNV genome-based DNA replicon vectors have the potential to induce stronger and longer expression of target antigens compared to conventional DNA vaccine vectors.

• 한국시뮬레이션학회논문지
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• 제15권4호
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• pp.1-10
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• 2006

컴퓨터 바이러스의 모델링 및 시뮬레이션에 관한 연구는 주로 네트워크 취약성 분석에 초점이 맞추어져 있었다. 그러나 컴퓨터 바이러스는 생물학적인 관점에서 분석되어 질 수 있다고 생각하여, 인공생명 기술을 이용하여 컴퓨터 바이러스를 분석하였다. 이 연구를 통해 컴퓨터 바이러스로 인해 네트워크에 미칠 영향과 행동 메커니즘을 이해할 수 있을 것이다. 본 논문에서는 인공생명을 이용한 컴퓨터 바이러스의 모델링 및 시뮬레이션 방법론을 제안한다. 이를 통해 컴퓨터 바이러스 백신의 연구에도 영향을 줄 수 있다.

• 생명과학회지
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• 제32권12호
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• pp.919-928
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• 2022

코로나-19 펜데믹에서 볼 수 있듯이, 새로운 바이러스 감염병의 출현은 전 세계적으로 공중보건에 심각한 우려를 발생시킨다. 특히, 항바이러스제 및 백신의 부재는 감염병의 피해를 더욱 증가시킨다. 식물 유래 천연물은 안전하고 효과적인 항바이러스제 개발의 주요 공급원이다. 본 연구는 한약재 식물의 에탄올추출물의 항바이러스 활성을 분석함으로써 안전성과 효능을 갖는 새로운 항바이러스제 후보물질을 발굴하는 것을 목표로 하였다. 10종의 한약재 에탄올추출물의 항산화활성과 세포독성을 분석한 후 로타바이러스, A형간염바이러스, 독감바이러스에 대한 광범위한 바이러스 사멸활성을 분석하였다. 특히, 마가목과 감초의 추출물은 독감바이러스에 대한 강력한 사멸활성을 나타내었다. 또한, 마가목과 감초의 추출물로 사멸된 독감바이러스의 백신효능과 방어효능을 마우스 모델에서 검증하였다. 추출물로 사멸된 바이러스는 높은 수준의 중화항체를 유도하였으며 야생형 바이러스 공격접종을 효과적으로 방어하는 우수한 백신효능을 나타내었다. 본 연구의 결과는 한약재 유래 천연물을 기반으로 하는 항바이러스제와 사백신 제조를 위한 바이러스 불활화제 개발에 활용될 수 있는 가능성을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.5917-5935
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• 2012

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

• 한국가금학회지
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• 제35권3호
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• pp.225-240
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• 2008

Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

• 대한바이러스학회지
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• 제28권4호
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• pp.303-316
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• 1998

An attenuated classical swine fever virus (CSFV), Suri strain, is a variant derived from a vaccine virus, LOM strain. This study was performed to elucidate the molecular biologcal properties of CSFV Suri strain, and to obtain the basic data for molecular epidemiological approaches for the disease. The truncated form of gp55 gene without the C-terminal transmembrane domain, in size of 1,023bp, was amplified by RT-PCR and sequenced by dye terminator cyclic sequencing method, and inserted into BamHI site of pAcGP67B baculovirus vector, establishing a cloned pAcHEG plasmid. By the nucleotide sequences determined, 341 amino acid sequences were predicted. As compared the nucleotide and amino acid sequences of gp55 of Suri with the various CSFV, Suri strain showed the high homology over 99.1% with ALD and LOM strains, but comparably the lower homology with Alfort and Brescia. In comparison of amino acid sequence in variable domain of gp55 protein, the similar tendency of homology was observed. In hydrophobicity analysis, all of four CSFV strains revealed the analogous patterns of hydrophobicity. The numbers and locations of N-glycosylation site and cysteine residues in gp55 were analyzed, those of Suri strain being coincident with ALD and LOM strains. The results suggest that gp55 in Suri strain has the high similarity to those in ALD and LOM strains in terms of the nucleotide and amino acid sequences and the functional properties of gp55 protein.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.242-254
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• 2018

Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express ${\alpha}$- and ${\beta}$-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the 'defensin vaccine' concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.