• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.108-113
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• 1994

Toxicity study of recombinant hepatitis B vaccine (LBD-008), a newly developed drug for acute and chronic hepatitis, was investigated in mice and guinea pigs. 1. Mice showed no production of antibodies against LBD-008 inoculated with aluminum hydroxide gel (Alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-008 only and of LBD-008 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-008 has no antigenic potential in mice or guinea pigs.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.110-116
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• 2000

Duck viral hepatitis is an acutic, highly infectious viral disease of young ducklings. The most practical means for controlling duck viral hepatitis is the vaccination of ducklings or of a breeding stock. We attempted to develop a vaccine strain of duck hepatitis virus (DHV) using a Korean isolate by serial chicken embryo passages. The propagation of DHV in chicken embryos was carried 140 passages. After the $50^{th}$ passage, of which the virus was non-pathogenic for ducklings, approximately every $20^{th}$ passage of the virus was tested for vaccinal efficacy. Both the $70^{th}$ and $90^{th}$ passage of the virus gave good protection against challenge infection to a DHV-DRL reference strain(type 1) and a virulent Korean isolate. The $110^{th}$, $125^{th}$ and $140^{th}$ passage of the virus were less protective than the $70^{th}$ and $90^{th}$ passage, which means that more than $110^{th}$ passage may lead to over-attenuation of the virus. Ducklings vaccinated with the chicken-embryo-adapted virus by oral, intramuscular or eye drop administration showed earlier resistance to challenge infection from 3 to 7 days postvaccination. Of the above methods, ducklings vaccinated intramuscularly presented the most rapid resistance against challenge. The minimum immune dose of the chicken-embryo-adapted virus in ducklings was also studied. Ducklings inoculated with a dose of $10^{2.0}\;ELD_{50}$ and below were not fully protected against challenge with a virulent DHV, showing a protection rate of 67% to 73%, but ducklings inoculated with a dose of $10^{3.0}\;ELD_{50}$ and over were completely protected. The virus yield of the chicken-embryo-adapted DHV was examined at 24hrs and 48hrs of the incubation time in the allantoic fluid, embryo head and embryo minus head of the embryonating egg. In all three components, the titer of the virus was higher at 48 hours than that at 24 hours after incubation. And the titer of the virus was higher in the embryo minus head, embryo head and the allantoic fluid, in order. Field trials for evaluating the efficacy of the attenuated DHV as a live vaccine were done in duck farms with about 25% mortality of flocks resulting from duck viral hepatitis. After the use of the experimental vaccine, the mortality due to duck viral hepatitis was dramatically reduced in the farms. These results indicated that the attenuated DHV using a Korean isolate could be a good candidate as a live vaccine strain of DHV in Korea.

• Animal cells and systems
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• v.3 no.3
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• pp.337-341
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• 1999

Hepatitis C virus (HCV) is a positive strand RNA virus of the Flaviviridae family and the major cause of post-transfusion non-A, non-B hepatitis. Vaccine development for HCV is essential but has been slowed by poor understanding of the type of immunity that naturally terminates HCV infection. The DNA-based immunization technique offers the potential advantage of including cellular immune responses against conserved internal proteins of a virus, as well as the generation of antibodies to viral surface proteins. Here, we demonstrate that cell lines expressing the HCV core and/or NS3 proteins can induce a specific CTL response in mice, and these results suggest a possibility that the HCV core and NS3 DNA can be used to induce CTL activity against the antigen in mice and can be further developed as a therapeutic and preventive DNA vaccine.

• Pediatric Infection and Vaccine
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• v.4 no.1
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• pp.106-115
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• 1997

Objective : To evaluate the immunogenicity and safety afforded by the HG-II$^{(R)}$ recombinant hepatitis B vaccine given to healthy neonates and children and to find the influence of preceding BCG vaccination on immunogenicity. Methods : Three doses of recombinant hepatitis B vaccine with a dose of $10{\mu}g$ were given at birth, 1 and 6 months of age. This study was conducted in three hospitals (Gyeongsang National University Hospital(Group A), Kangnam General Hospital(Group B) and Younsei University Hospital(Group C)) from April, 1995 to June, 1996. Group A and Group B received 2nd dose of hepatitis B vaccine at 1 week after and before BCG vaccine, respectively. Antibidy levels, at 1 month after the 3rd dose of hepatitis B vaccine were determined by a radioimmunoassay. Results : 1) One hundred four infants and ten children were enrolled : 55 infants and 43 infants received 2nd dose of hepatitis B vaccine at 1 week after( After BCG Group) and before BCG vaccine(Before BCG Group), respectively. 2) The seropositive rate was 99.1%, and geometric mean anti-HBs titer was 131.2mIU/ml. 3) The geometric mean titers were 105.5mIU/ml and 162.8mIU/ml in After BCG and Before BCG Group, respectively(p<0.025). 4) Among 359 episodes of vaccination, the occurrence of systemic and local side reaction were reported in 7.8% and 1.4%, respectively. Conclusion : Recombinant hepatitis B vaccine(HG-II$^{(R)}$))was highly immunogenic and safe. The significantly lower geometric mean antibody titer in the BCG preceding group was observed. Well-designed controlled study with the large number of sample size will be required to show the influence of preceding BCG vaccination.

• Biomolecules & Therapeutics
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• v.7 no.4
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• pp.390-396
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• 1999

CJ-50005 is a hepatitis A vaccine which is prepared by formalin inactivation of the HM175 virus cultured in human diploid MRC-5 cells. The general pharmacological properties of CJ-50005 were evaluated in various animals and in vitor system. CJ-50005 at the doses of 0.025, 0.25 and 0.75 $\mu\textrm{g}$/kg, i.m. had no effect on general behavior in mice, chemo- and electro-convulsions in mice, writhing syndrome induced by acetic acid in mice, the barbital sleeping time in mice, body temperature in rats, charcoal meal propulsion in mice and urine and electrolytes excretion in rats. In anesthetized dogs, CJ-50005(0.25 and 0.75 $\mu\textrm{g}$/kg, i.v) did not alter the respiratory rate, blood pressure, heart rate, femoral blood flow and ECG. In in vitro experiment, CJ-50005 at the concentration up to 0.02 $\mu\textrm{g}$/ml did not produce any changes in the contractions of the isolated ileum of guinea pigs caused by acetylcholine, histamine or $BaCl_2$. Since these pharmacological effects of CJ-50005 were observed at dose much greater than those in clinical use (approximately 0.025 $\mu\textrm{g}$/kg, i.m.), it is likely that this vaccine may be relatively free of undesirable effects in clinical practice.

• Toxicological Research
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• v.9 no.2
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• pp.225-232
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• 1993

SCi-B-Vac, the 3rd hepatitis B vaccine , was selected for clinical evaluation on the basis of toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, organs which are mainly affected, and to estimate its lethality in mice and rats given Sci-B-Vac through two routes of administratin. In male and female rats given a single intragastrical dose of Sci-B-Vac, we estimated that $LD_{50}$ values were over 2.00 ml/100g B.W. (10ng/ml), respectively.

• Clinical and Experimental Vaccine Research
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• v.12 no.1
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• pp.47-59
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• 2023

Purpose: The development and study of hepatitis C virus (HCV) vaccine candidates' individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice. Materials and Methods: HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes' CD4⁺ and CD8⁺ T-lymphocytes was assessed. Results: Donors' PBMCs showed different levels of EC expression, ranging between 0.83-2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4⁺ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8⁺ T-cells % was observed (p=0.89). Conclusion: The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals' antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4⁺ T-cell early priming.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1335-1343
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• 2022

COVID-19 is an emerging disease that poses a severe threat to global public health. As such, there is an urgent demand for vaccines against SARS-CoV-2, the virus that causes COVID-19. Here, we describe a virus-like nanoparticle candidate vaccine against SARS-CoV-2 produced by an E. coli expression system. The fusion protein of a truncated ORF2-encoded protein of aa 439~608 (p170) from hepatitis E virus CCJD-517 and the receptor-binding domain of the spike protein from SARS-CoV-2 were expressed, purified and characterized. The antigenicity and immunogenicity of p170-RBD were evaluated in vitro and in Kunming mice. Our investigation revealed that p170-RBD self-assembled into approximately 24 nm virus-like particles, which could bind to serum from vaccinated people (p < 0.001) and receptors on cells. Immunization with p170-RBD induced the titer of IgG antibody vaccine increased from 14 days post-immunization and was significantly enhanced after a booster immunization at 28 dpi, ultimately reaching a peak level on 42 dpi with a titer of 4.97 log₁₀. Pseudovirus neutralization tests showed that the candidate vaccine induced a strong neutralizing antibody response in mice. In this research, we demonstrated that p170-RBD possesses strong antigenicity and immunogenicity and could be a potential candidate for use in future SARS-CoV-2 vaccine development.

• Pediatric Infection and Vaccine
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• v.20 no.3
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• pp.147-160
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• 2013

Purpose: Although the overall incidence of hepatitis A in Korea has been decreasing recently, the adolescents born before the introduction of the hepatitis A vaccine remain to be highly vulnerable to outbreak. This study examines the unvaccinated adolescents' and their parents' knowledge and health beliefs toward hepatitis A vaccination. Methods: Healthy adolescents aged 13-19 years old who had no previous history of hepatitis A vaccine and hepatitis A infection, and their parents or legal guardians were the subjects of the study. The survey was conducted using a structured questionnaire based on the Health Belief Model, and examined the subjects' demographics, knowledge, and health beliefs (i.e., perceived susceptibility, severity, benefits, and barriers). Results: We included 157 adolescents and their parents/guardians (mean age: $16.0{\pm}1.6$ and $45.6{\pm}4.7$ years, respectively). The average knowledge item score for adolescents and parents was $6.4{\pm}3.7$ and $7.3{\pm}3.4$ (out of 18), respectively. Similarly, average Health Belief Model item scores were: susceptibility, $5.6{\pm}1.6$ and $5.9{\pm}1.7$ (range: 2-10); severity, $16.3{\pm}4.1$ and $18.3{\pm}3.6$ (range:5-25); benefits, $19.7{\pm}3.3$ and $20.6{\pm}2.1$ (range:5-25); and barriers, $41.3{\pm}8.9$ and $39.0{\pm}9.1$ (range:7-85). The major reason for not undergoing hepatitis A vaccination was lack of knowledge about its importance. Conclusions: Refresher health lectures about hepatitis A and the vaccine are needed by both the adolescents and their parents. Furthermore, the inclusion of hepatitis A vaccine in the national immunization program should be considered to reduce the risk of hepatitis A outbreak and to raise the vaccination coverage among the adolescents in Korea.

• Toxicological Research
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• v.17 no.4
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• pp.297-301
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• 2001

The acute toxicity of CJ-50005, an inactivated whole virus vaccine derived from hepatitis A virus (HM175) grown in human MRC-5 diploid fibroblast culture, was tested in Sprague Dawley (SD) rats and beagle dogs. CJ-50005 was orally and intramuscularly administered up to the maximum dose of 81$\mu\textrm{g}$/kg. as much as 3,000 times of the expected clinical dose, in SD rats and was intramuscularly administered up to 27 $\mu\textrm{g}$/kg, as much as 1,000 times of the expected clinical dose, in beagle dogs. In these experiments, there were no death and clinical changes which were related to CJ-50005 administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of CJ-50005 over 81$\mu\textrm{g}$/kg in SD rats and over 27$\mu\textrm{g}$/kg in beagle dogs was proved to be safe, and it is thought that CJ-50005 may not show any toxicity in its clinical use.