• KSBB Journal
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• v.26 no.6
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• pp.491-504
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• 2011

This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLR-independent and TLR-dependent adjuvants), and heat- and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.

• Journal of Life Science
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• v.32 no.12
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• pp.919-928
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• 2022

As seen in the COVID-19 pandemic, unexpected emergence of new viruses presents serious concern on public health. Especially, the absence of effective vaccines or antiviral drugs against emerging viruses significantly increases the severity of disease and duration of viral circulation among population. Natural products have served as a major source for safe and effective antiviral drugs. In this study, we examined the virucidal activity of medical herb extracts with a view to discover novel antiviral agents with desired levels of safety and antiviral efficacy. Ethanol extracts of ten selected medical herbs were tested for antioxidant activity and in-vitro cytotoxicity in various animal cell lines. Of note, the herbal extracts showed broad and potent virucidal activities against rotavirus, hepatitis A virus, and influenza A virus. The extracts of Sorbus commixta and Glycyrrhiza uralensis showed strong virucidal activities against influenza A virus. We also examined whether the extracts of Sorbus commixta and Glycyrrhiza uralensis can be used as inactivating agents to prepare an inactivated viral vaccine. In a mouse model, influenza A virus inactivated by the extracts elicited high levels of neutralizing antibodies, and the vaccination provided complete protection against lethal challenge. These results suggest that herb-derived natural products can be developed to antiviral drugs as well as inactivating agents for preparation of inactivated viral vaccines.

• Journal of Ginseng Research
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• v.36 no.4
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• pp.396-402
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• 2012

Vaccination is the main strategy for preventing influenza infection. However, vaccine efficacy is influenced by several factors, including age and health status. The efficacy of the influenza vaccine is much lower (17% to 53%) in individuals over 65 yr of age compared with young adults (70% to 90%). Therefore, increasing vaccine efficacy remains a challenge for the influenza vaccine field. In this study, we investigated the impact of supplementing vaccination with the dietary intake of Korean red ginseng (RG) extract and RG saponin. Mice were immunized two times intranasally with inactivated influenza A (H1N1) virus. Mice received RG extract or RG saponin orally for 14 d prior to the primary immunization. After the primary immunization, mice continued to receive RG extract or RG saponin until the secondary immunization. Mice vaccinated in combination with dietary intake of RG extract and RG saponin showed elevated serum anti-influenza A virus IgG titers and improved survival rates in lethal influenza A virus infection: 56% and 63% of mice receiving RG extract or RG saponin survived, respectively, while 38% of mice that only received the vaccine survived. Moreover, mice receiving RG extract supplementation recovered their body weight more quickly than those not receiving RG extract supplementation. We propose that the dietary intake of RG extract and RG saponin enhances the vaccine-induced immune response and aids in providing protection against influenza virus infection.

• The Journal of the Korean Society for Microbiology
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• v.16 no.1
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• pp.83-89
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• 1981

Japanese encephalitis has been prevalent for long time in the Far East and many patients have been reported in both South East and Mid-West Asia recently. Recently, vaccine was used in prevention of this viral disease of man which was derived from formalin inactivated virus inoculated into mouse brain, but live attenuated active vaccine for human is not developed yet. Author inoculated Japanese encephalitis virus into several cell culture strains for development of live attenuated encephalitis virus strain and the results were as follows: 1. Japanese encephalitis virus was inactivated rapidly in cell free medium at $36^{\circ}C$ and totally inactivated by 72 hours. 2. In growth curve of Japanese encephalitis virus in HeLa cell cultures, maximal multiplication of the virus was occured at 4th day and virus multiplication was continued for at least 12 days. 3. After succeeding passage of the virus in HeLa cell cultures and human esophagus epithelial cell cultures, infectivity of virus for mice was disappeared from 2nd passage in HeLa cell cultures and 3rd passage in esophagus epithelial cell cultures. 4. In inoculation to monkey kidney epithelial cells and chick embryo cell cultures, infectivity of the virus for mice was continued after 10th passages.

• Clinical and Experimental Vaccine Research
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• v.13 no.2
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• pp.155-165
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• 2024

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.55-67
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• 2005

Cancer vaccine is an active immunotherapy to stimulate the immune system to mount a response against the tumor specific antigen. Working as a stimulant to the body's own immune system, cancer vaccines help the body recognize and destroy targeted cancers and may help to shrink advanced tumors. Research is currently underway to develop therapeutic cancer vaccines. It is also possible to develop prophylactic vaccines in the future. The whole cell approach to eradicate cancer has used whole cancer cells to make vaccine. In an early stage of this approach, whole cell lysate or a mixture of immunoadjuvant and inactivated cancer cells has been used. Improved vaccines are being developed that utilize cytokines or costimulatory molecules to mount an attack against cancer cells. In case of melanoma, these vaccines are expected to have a therapeutic effect of vaccine. Furthermore, it is attempting to treat stomach cancer, colorectal cancer, pancreatic cancer, and prostate cancer. Other vaccines are being developing that are peptide vaccine, recombinant vaccine and dendritic cell vaccine. Out of them, reintroduction of antigen-specific dendritic cells into patient and DNA vaccine are mostly being conducted. Currently, research and development efforts are underway to develop therapeutic cancer vaccine such as DNA vaccine for the treatment of multiple forms of cancers.

• Journal of Veterinary Science
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• v.22 no.3
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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.

• Molecules and Cells
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• v.42 no.12
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• pp.869-883
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• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• Korean Journal of Veterinary Research
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• v.45 no.2
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• pp.215-221
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• 2005

Canine coronavirus (CCV) causes a mild gastroenteritis in dogs. The virus is highly contagious. Although the virus was isolated more than thirty years ago, canine coronavirus infection continues to be a widespread problem. Mixed infections with both CCV and canine parvovirus (CPV) are common. Four kinds of commercial killed CCV vaccines are available in Korea. All the commercial vaccines should pass the National Assay for Veterinary Biologicals prior to release. For the potency test of CCV vaccine, it is necessary to use CCV antibody free dogs. The test requires not only kennels but high cost. To develop easy, efficient and economic potency test method for killed CCV vaccine using laboratory animals, a series of experiments with rabbits and guinea pigs were carried out in this study. In the preliminary test, the guinea pigs showed better immune responses than rabbits. The guinea pig was also easy to manage. So guinea pig was selected for the potency test animals. When the guinea pigs were inoculated twice with one dose of vaccine intramuscuarly each, slower and a little lower SN antibody titers were induced in guinea pigs than in dogs (about 2 kg body weight Beagle strain) given the same posology as guinea pigs'. It was concluded that guinea pigs could be substituted for dogs in the potency test of killed CCV vaccine.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.54 no.5
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• pp.652-659
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• 2021

Microorganism-derived compounds, such as peptidoglycan, lipoteichoic acid, and β-glucan were supplemented in the scuticociliate Miamiensis avidus (M. avidus) vaccine to verify the specify component contribution to the adjuvant effect. Vaccine was formulated with the inactivated M. avidus antigen (YS2, 4.44×10⁵ cells/fish) in combination with either peptidoglycan (10 ㎍ and 100 ㎍/fish), lipoteichoic acid (5 ㎍ and 50 ㎍/fish), or β-glucan (10 ㎍ and 100 ㎍/fish). Olive flounder injected with peptidoglycan supplemented vaccine (10 ㎍ and 100 ㎍/fish) exhibited significant protection, and the relative percent survival (RPS) was 55% and 65% at 4 weeks post vaccination (wpv), respectively, at the corresponding doses. The vaccine groups with added lipoteichoic acid (5 ㎍ and 50 ㎍/fish) exhibited RPS of 40% and 5%, respectively. Additionally, the group with added β-glucan (100 ㎍/fish) exhibited RPS of 35%, but no effect was observed in the group with added 10 ㎍/fish β-glucan. At 8 wpv, olive flounder injected with peptidoglycan and lipoteichoic acid supplemented vaccines exhibited protection with RPS range of 11/11% and 5/21%, respectively, at the respective doses. M. avidus vaccine containing 10 ㎍ and 100 ㎍/fish of β-glucan exhibited the RPS of 32% and 37%, respectively. Conclusively, peptidoglycan contributed in high protection of the M. avidus vaccine, and thus, it can be used as an effective adjuvant in the M. avidus vaccine.