• Biomolecules & Therapeutics
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• 제10권2호
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• pp.124-128
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• 2002

Hantaan (HTN) and Puumala (PUU) viruses are major etiological agents of hemorrhagic fever with renal syndrome (HFRS), an important public health problem in Korea after the Korean War. The objective of present study was to determine allergenic potency of an inactivated combination vaccine against HTN and PUU viruses inflection. As a series of allergenicity assessment, a homologous active systemic anaphylaxis (ASA) and homologous/heterologous passive cutaneous anaphylaxis (PCA) tests using the mice and guinea pigs were carried out. In the ASA test, no anaphylactic symptoms were observed in the guinea pigs sensitized with the vaccine alone as well as the vaccine emulsified with an adjuvant. By homologous PCA test, the vatscine did not induced the potential IgE antibody production in the sera obtained from the sensitized guinea pigs. In addition, IgE against the vaccine was not significantly enhanced from the mice inoculated with the vaccine, which was judged by the heterologous PCA test in rats. On the other hand, the inoculation of ovalbumin appeared to allergenic reactions both in the ASA and PCA tests. The results suggest that a combination vaccine against HW and PUU viruses have no allergenic potential in mice or guinea pigs.

• 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.

• 대한바이러스학회지
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• 제26권1호
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• pp.67-76
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• 1996

The methods that make Hantavirus grow consist of inoculation into the experimental animals and cultured cells. The cultured cells, such as Vero-E6 and A549 cells, have been usually used for isolation of the virus and the animals, such as mice and rats, are used for large scale preparation of the virus so far. Furthermore, the cell can be used to maintain the virus and assay the infectivity and the animals can be used for the experiment of viral pathogenicity and challenge for assessment of vaccine. Apodemus mice, the own natural host of the virus, has been used for challenge test of Hantaan virus. However it has been pointed out to difficult handling and breeding the animal in laboratory. Therefore, we attempted to establish a new animal model for challenge test at the time of isolation of Maaji virus which is a new hantavirus similar but distinct to Hantaan virus. In suckling hamster, the titer of Maaji virus and the lethality to mice of the virus were increased gradually in the titer and lethality through passage by intracerebral (IC) inoculation. We tried to re-adapt this brain virus to lung of weanling hamster. The brain passaged virus was inoculated into weanling hamster intramuscularly. Again, the titer of the virus in lung was also increased by continuous passage of this virus. This facts could regarded as adaptation to new environment in which the virus proliferates. To identity the virus passaged in hamster with Maaji virus, both of the virus passaged in hamster brain and lung were compared with Maaji virus (MAA-I) and Hantaan virus (HTN 76-118) by means of restriction fragment length polymorphism (RFLP) and slingle strand conformation polymophism (SSCP). As a result, we conclude that Maaji virus could be adapted successfully to weanling hamster through this passage strategy. Utilizing this adapted Maaji virus strain, hamster model is able to be used for challenge test in hantaviral vaccinology and further experiments utilizing hamster system as a rather available and convenient lab animal are expected.

• Journal of Microbiology
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• 제43권6호
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• pp.537-545
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• 2005

Even though neutralizing antibodies against the Hantaan virus (HTNV) has been proven to be critical against viral infections, the cellular immune responses to HTNV are also assumed to be important for viral clearance. In this report, we have examined the cellular and humoral immune responses against the HTNV nucleocapsid protein (NP) elicited by virus infection or DNA vaccination. To examine the cellular immune response against HTNV NP, we used $H-2K^b$ restricted T-cell epitopes of NP. The NP-specific $CD8^+$ T cell response was analyzed using a $^{51}Cr-release$ assay, intracellular cytokine staining assay, enzyme-linked immunospot assay and tetramer binding assay in C57BL/6 mice infected with HTNV. Using these methods, we found that HTNV infection elicited a strong NP-specific $CD8^+$ T cell response at eight days after infection. We also found that several different methods to check the NP-specific $CD8^+$ T cell response showed a very high correlation among analysis. In the case of DNA vaccination by plasmid encoding nucleocapsid gene, the NP-specific antibody response was elicited $2\~4$ weeks after immunization and maximized at $6\~8$ weeks. NP-specific $CD8^+$ T cell response reached its peak 3 weeks after immunization. In a challenge test with the recombinant vaccinia virus expressing NP (rVV-HTNV-N), the rVV-HTNV-N titers in DNA vaccinated mice were decreased about 100-fold compared to the negative control mice.

• 대한바이러스학회지
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• 제29권2호
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• pp.55-64
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• 1999

In Yugoslavia, hemorrhagic fever with renal syndrome (HFRS) is one of the important national health problem, but no vaccine has been used to prevent HFRS. Since first HFRS case in 1952, sporadic cases of HFRS occurred every year and over 4,000 registered cases with $1{\sim}16%$ mortality so far. We performed a prospective, randomized double-blind placebo-controlled trial to evaluate the effectiveness of $Hantavax^{TM}$ against HFRS in 3,900 healthy adults living in the endemic areas of Yugoslavia. 1,900 people were given 0.5 ml of Hantavax subcutaneously twice at one month interval and a booster shot at one year after. For controls other 2,000 healthy people were given 0.5 ml of physiolosical saline as a placebo. We investigated HFRS cases in both the vaccinated and nonvaccinated groups by monitoring the program for patient registration in the areas from 1996 to 1998, and the effect of vaccine was analyzed epidemiologically. No confirmed case of HFRS was observed among 1,900 Hantavax vaccinees, while 20 confirmed cases were observed among 2,000 nonvaccinated control group. There were no remarkable side effects among the vaccinees either locally or in general after inoculation of the vaccine. The Hantavax vaccine showed statistically significant protective efficacy against HFRS among Yugoslavian people.

• 한국군사과학기술학회지
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• 제24권3호
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• pp.348-355
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• 2021

Hantaan virus(HTNV) causes hemorrhagic fever with renal syndrome(HFRS) with a case fatality rate ranging from <1 to 15 % in human. Hantavax^Ⓡ is a vaccine against the Hantavirus, which has been conditionally approved by the Ministry of Food and Drug Safety(MFDS). However, only 50 % of volunteers had neutralizing antibodies 1 year following the boost. Effective antiviral treatments against HTNV infection are limited. Hantaviruses generally cause asymptomatic infection in adult mice. On the other hand, infection of suckling and newborn mice with hantaviruses causes lethal neurological diesease or persistant infection, which is different from the disease in humans. The development of vaccines and antiviral strategies for HTNV has been partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this report, we established a lethal mouse model for HTNV, which may facilitate in vivo studies on the evaluation of candidate drugs against HTNV. The median lethal dose value of HTNV was calculated by probit analysis of deaths occurring within two weeks. Five groups of ten ICR mice were injected intracranially with serial 2-fold dilutions (from 50 to 3.125 PFU/head) of HTNV. Mice injected with HTNV began to die at 8 days post-infection. The lethal dose required to kill 50 % of the mice (LD₅₀) was calculated to be 2.365 PFU/head.

• Kidney Research and Clinical Practice
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• 제37권4호
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• pp.366-372
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• 2018

Background: An inactivated Hantaan virus vaccine (iHV) has been broadly used as a preventive strategy for hemorrhagic fever with renal syndrome (HFRS) by the South Korean Army. After the vaccination program was initiated, the overall incidence of HFRS cases was reduced in the military population. While there are about 400 HFRS cases annually, few studies have demonstrated the efficacy of the iHV in field settings. Therefore, this study aimed to evaluate the iHV efficacy on HFRS severity. Methods: From 2009 to 2017, HFRS cases were collected in South Korean Army hospitals along with patients' vaccination history. HFRS patients were classified retrospectively into two groups according to vaccination records: no history of iHV vaccination and valid vaccination. Vaccine efficacy on the severity of acute kidney injury (AKI) stage and dialysis events were investigated. Results: The effects of the iHV on renal injury severity in between 18 valid vaccinated and 110 non-vaccinated patients were respectively evaluated. In the valid vaccination group, six of the 18 HFRS patients (33.3%) had stage 3 AKI, compared to 60 of the 110 (54.5%) patients in the non-vaccination group. The iHV efficacy against disease progression ($VE_p$) was 58.1% (95% confidence interval, 31.3% to 88.0%). Conclusion: The iHV efficacy against the progression of HFRS failed to demonstrate statistically significant protection. However, different severity profiles were observed between the iHV and non-vaccination groups. Additional studies with larger populations are needed to demonstrate the effectiveness of the iHV in patients with HFRS.