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신증후출혈열 환자의 혈청학적 및 분자생물학적 진단 검사법 비교
우영대(Young-Dae Woo),문희주(Hi-Joo Moon),배형준(Hyung-Joon Bae) 대한의생명과학회 2000 Biomedical Science Letters Vol.6 No.2
우리 나라에서 발생하고 있는 급성 출혈성 질환인 신증후출혈열의 원인 바이러스는 Family Bunyaviridae의 Genus Hantavirus에 속하는 한탄과 서울바이러스에 의하여 발생되고 있다. 본 연구에서는 신증후출혈열로 의뢰된 환자에서 한탄바이러스에 대한 항체가를 간접면역형광항체법 (indirect immunofluorescent antibody technique, IFAT), 면 역효소측정법 (enzyme-linked immunosorbent assay, ELISA) (IgG, IgM), 고비중입자응집반응 (high density composite particle agglutination, HDPA) 및 플라크감소중화시험 (plaque reduction neutralization test, PRNT) 등으로 비교 측정하였고, 신증후출혈열 환자로 확진된 15명의 한타바이러스 혈청형을 PRNT와 혈청형 특이 역전사 효소 중합효소연쇄반응 (nested reverse transcriptase polymerase chain reaction, nested RT-PCR)으로 확인하였다. 신증후출혈열로 의뢰된 환자에서의 한탄바이러스에 대한 IFAT, ELISA (IgG, IgM), HDPA 그리 고 PRNT 비교에서 형광항체, ELISA IgG, 응집항체 및 중화항체는 8명 모두 높게 나타났으며, ELISA IgM은 5명에서는 현저히 높은 항체를 보유하고 있었다. 신증후출혈열 환자 15명에서는 높은 형광항체와 중화항체 역가를 나타내었고, 15명 중 12명은 한탄바이러스, 2명은 서울바이러스에 대한 높은 중화항체를 갖고 있었으며, 1명은 두 바이러스에 대하여 통일한 항체 역가를 나타내었으며, 혈청형 특이 primer를 사용한 nested RT-PCR에서는 15명 중 3명과 1명만이 한탄바이러스와 서울바이러스 primer에 대해 RNA가 검출되었다. The etiologic agents of haemorrhagic fever with renal syndrome (HFRS) in Korea are Hantaan and Seoul virus in the genus Hantavirus, family Bunyaviridae. Antibody titers of sera from HFRS patients against Hantaan virus were measured by immunofluorescent antibody technique (IFAT), enzyme-linked immunosorbent assay (ELISA), high density composite particle agglutination (HDPA) and plaque reduction neutralization test (PRNT). PRNT and nested reverse transcriptase polymerase chain reaction (nested RT-PCR) was used for serotypic differentiation of Hantaviruses against Hantaan and Seoul virus. Eight doubtful HFRS patients showed higher fluorescent, IgG ELISA, agglutination and neutralizing antibody titer by IFAT, ELISA IgG, HDPA and PRNT, respectively. Five out of them showed high IgM antibody titer by IgM capture ELISA against Hantaan virus, remarkably. Fifteen HFRS patients showed higher fluorescent antibody titer by IFAT. In PRNT, 12 out of them showed high neutralizing antibody titer aginst HTNV, 2 against SEOV and 1 against both viruses. In nested RT-PCR using serotype specific-primer, 3 out of them showed positive against HTNV and 1 against SEOV.
우영대(Young Dae Woo),주용규(Yong Gyu Joo),백락주(Rak Joo Baek),이호왕(Ho Wang Lee) 대한바이러스학회 2000 Journal of Bacteriology and Virology Vol.30 No.1
Since Hantavax, formalin inactivated Hantaan virus vaccine (10,240 ELISA units/ml), has been developed in 1990 to prevent against haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan or Seoul virus, it has been commercially available in Korea. Twenty-one healthy people were booster shot once and twice after prirnary basic vaccination with Hantavax. Seroconversion rates were measured by immunofluorescent antibody technique (IFAT), enzyme-linked immunosorbent assay (ELISA), high density composite particle agglutination (HDPA), and plaque reduction neutralization test (PRNT). Seroconversion rates of 21 vaccinees at one year after primary basic vaccination were 52.3%, 95.2%, 0.0%, 47.6%, and 28.6%, and 13 vaccinees at one month after 1st booster vaccination were 100%, 100%, 30.7%, 100% and 100% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Seroconversion rates declined slightly by twenty months, and they were 84.6%, 92.3%, 0.0%, 84.6% and 69.2% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Seroconversion rates of 9 vaccinees at three months after 2nd booster vaccination were 100%, 100%, 0.0%, 100%, and 88.9%, and 16 vaccinees at one year after the 2nd booster vaccination were 87.5%, 93.8%, 0.0%, 87.5% and 81.3% by IFAT, ELISA (IgG, IgM), HDPA and PRNT, respectively. Based on the above result Hantavax has proved a vigorous anamnestic response after the 1st and the 2nd booster vaccination and has persisted higher fluorescence, agglutination and neutralizing antibody titers in vaccinees.
$1996{\sim}1998$년 유고슬라비아에서 실시한 한탄바이러스 불활화 백신($Hantavax^{TM}$)의 면역효과에 대한 야외시험
주용규,우영대,안창남,김훈,장양석,박승철,김민자,이은실,이호왕,Chu, Yong-Kyu,Gligic, Anna,Tomanovic, Snezana,Bozovjc, Boyana,Obradovic, Mirceta,Woo, Young-Dae,An, Chang-Nam,Kim, Hun,Jiang, Yang-Seok,Park, Seung-Chul,Kim, Min-Ja 대한미생물학회 1999 Journal of Bacteriology and Virology Vol.28 No.1
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.
한국산 가토에서의 Shope Fibroma Virus에 대한 항체증명과 섬유종 형성에 관한 연구
양현옥,박건우,류선자,우영대,주용규,이호왕,Yang, Hyun-Ok,Park, Kun-Koo,Ryu, Sun-Ja,Woo, Young-Dae,Joo, Yong-Kyu,Lee, Ho-Wang 대한미생물학회 1998 Journal of Bacteriology and Virology Vol.28 No.4
In our preliminary study to find antiviral or antitumor agents from Korean natural products, we found that the Shope fibroma virus (SFV) induced fibromas reaching maximum size at $5{\sim}6$ days with spontaneous disappearance at $15{\sim}20$ days after SFV intracutaneous inoculation into Korean domestic rabbits. However, the sizes of fibromas of rabbits at day 5 after virus inoculation were significantly different individually. Assuming that the variation of tumor size was due to either susceptibility or the preexisting antibodies against SFV in the Korean domestic rabbits, the rabbits were checked for the antibodies against SFV by IFAT using SFV infected RK13 cells. The antibody positive rate of normal Korean domestic rabbits was 32.8% and the sizes of the fibromas of the positive rabbits were significantly smaller than those of negative rabbits (p<0.0001). The fibroma sizes were dependent on the antibody titers of rabbits to SFV. The sizes of fibromas after inoculation of SFV into immunized rabbits were about one tenth of those by the first inoculation into normal rabbits. This is the first report on the antibody prevalence against SFV among normal Korean domestic rabbits and it suggest the existence of a wild fibroma virus or related virus in Korea.
1996~1998년 유고슬라비아에서 실시한 한탄바이러스 불활화 백신 ( Nantavax<sup>TM</sup>) 의 면역효과에 대한 야외시험
주용규(Yong Gyu Joo),Anna Gligic,Snezana Tomanovic,Boyana Bozovjc,Mirceta Obradovic,우영대(Young Dae Woo),안창남(Chang Nam Ahn),김훈(Hoon Kim),장양석(Yang Suk Jang),박승철(Seung Chul Park),김민자(Min Ja Kim),이은일(Eun Il L 대한바이러스학회 1999 Journal of Bacteriology and Virology Vol.29 No.2
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∼16% mortality so far. We performed a prospective, randomized double-blind placebo-controlled trial to evaluate the effectiveness of Hantavax 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.