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$1996{\sim}1998$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.
1985년 한국에서 발생한 Scrub Typhus 환자의 혈청진단 및 임상역학적 조사
주용규,富山 哲雄,전성주,김민자,박승철,최경열,김연수,이호왕 대한감염학회 1988 감염 Vol.20 No.2
Serological studies were performed on the 2,135 sera from the suspected Hemorrhagic fever with renal syndrome patients in 1985 and 64 scrub typhus patients were diagnosed serologically. Serotypes of etiologic agents, epidemiology and clinical features of the patients with scrub typhus were analyzed. The results were summarized as follows. 1) Among the 64 patients were infected with Rickettsia tsutsugamushi Karp type, 22 patients were infected with Gilliam type and only two patients were infected with Kato type. The remaining 16 patients had antibodies against more than two serotypes of R. tsutsugamush at the same time. 2) The regional occurrence of the patients showed that 33 patients occurred in Kyunggi province and the remaining patients were occurred in all over the Korea. 3) Fifty three of the 64 patients were female and 11 were male. More than a half of the patiens were in age groups of 50-70. 4) As the clinical features, most of the patients showed fever, chill, general weakness and myalgia however, abdominal pain, sputum and dyspnea were not uncommon. Clinical signs such as tachycardia, tachypnea, pharyngeal and conjunctival injection and abdominal tenderness were common but hepatomegaly, hypotension, rales, and edema were uncommon. 5) The laboratory findings showed frequently elevation of transaminase and abnormal chest X-ray, and leukocytosis, thrombocytopenia and abnormal urinary sedimetns were not uncommon. 6) Most of the patients showed one to three weeks of fever and then gradual improvement, but two were died of pulmonary edema. 7) Because most of the patients occurred in autumn, during the epidemic season of HFRS and leptospirosis, the differential serologic diagnosis among the diseases is absolutely demanded.
신증후출혈열 백신 한타박스 접종자에서의 면역반응 및 항체지속 기간에 관한 연구
우영대,주용규,이호왕 대한감염학회 1998 감염 Vol.30 No.4
목 적 : 우리나라에서 한탄바이러스와 서울 바이러스에 의하여 발생하는 신증후출혈열을 예방하기 위하여 1990년 개발된 한타박스는 현재 상용화되어 있다. 한타박스가 시중에서 상용화되어 사용된 역사가 짧으므로, 예방접종자에서 항체지속기간에 관한 연구는 미흡한 실정이다. 본 연구에서는 신증후출혈열 예방백신인 한타박스를 접종한 사람들에서의 항체 특히 중화항체양전율과 항체지속기간을 조사하고자 하였다. 방 법 : 아산생명과학연구소에 근무하는 61명의 연구원들을 대상으로 신증후출혈열 예방백신인 한타박스를 한달간격으로 2회 기본접종하였다. 예방백신을 접종하기 전 대상자들이 혈청을 채취하여 한탄바이러스와 서울바이러스에 대한 항체음성임을 형광항체법과 중화항체법으로 확인하였다. 한타박스를 기본접종한 한달 후 및 일년 후 그리고 기본 접종한지 일년이 경과하여 1차 부스터 접종을 한 한달 후 및 2년여가 경과한 후와 2차 부스터 접종 한달 후의 백신접종자에서의 항체양성율 및 항체가를 간접면역형광항체법(IFA), 고비중입자응집반응(HDPA) 및 플라크감소 중화시험(PRNT) 등으로 비교 측정하여 배신접종자에서의 항체양성율, 형광항체가 및 중화항체가와 면역지속기간을 조사하였다. 결 과 : 1) 신증후출혈열 백신인 한타박스를 2회 기본접종을 하고 한달 후 혈청을 채취한 21명에서의 IFA, HDPA와 PRNT방법에 의한 항체양성율은 각각 20/21 (95.2%), 19/21 (90.5%), 14/21 (66.7%)이었으며, 평균 항체역가는 각각 262,248,120이었다. 2) 기본접종 1면 후 혈청을 채취한 40명에서의 IFA, HDPA와 PRNT방법에 의한 항체양성율은 저하되어 각각 25/40 (62.5%), 18/40 (45.0%) 그리고 9/40 (22.5%)이었으며 평균 항체역가는 각각 92,41,24.5 이었다. 3) 부스터접종이 효과를 조사하여 본 결과 기본접종 1년후 채혈한 14명에서의 IFA와 PRNT방법에 의한 항체양성율은 7/14 (50.0%), 3/14 (21.4%)이었으며 평균 항체역가는 각각 100.6, 47.1 이었다. 1차 부스터 접종 한 14명중 1개월후 채혈한 8명의 IFA와 PRNT방법에 의한 항체양성율은 8/8(100%), 8/8(100%)이었으며 평균 항체역가는 각각 852,182.5 이었다. 1차 부스터 접종한 20개월후 채혈된 12명의 항체양성율은 11/12 (91.7%), 9/12 (75.0%)이었으며 평균 항체역가는 각각 296, 33.3 이었고, 2차 부스터 접종한 3개월 후 채혈한 7명의 항체양성을율은 7/7 (100%), 6/7(85.7%)으로 항체 평균역가는 각각 548,46 이었따. 기본접종 1년후 1차부스터접종을 실시한 1개월후 채혈한 8명의 항체역가와 2차부스터접종을 실시한 한달후 채혈한 7명의 항체역가를 형광항체법과 중화항체법으로 조사한 결과 뚜렷한 항체역가의 증가를 나타내는 기왕성면역반응을 볼 수 있었다. 결 론 : 백신접종자에서 한탄바이러스에 대한 항체를 높게 유지하기 위해서는 2회의 기본접종과 기본접종 1년후 추가접종이 필요하며, 추가접종후 최소한 2년간은 항체가 지속적으로 유지된다는 사실을 증명하였다. Background : Hantavax™ was developed and has been used for prevention of hemorrhagic fever with renal syndrome caused by Hantaan and Seoul virus since 1990 in Korea. Since Hantavax™ has short usage history, the duration of antibodies persistancy in vaccinees was not well studied. Methods : Hantavax™ was inoculated to 61 people who work at Asan Institue for Sciences twice subcutaneously at one month interval according to the manufacturer's recommendation. Antibody titers of vaccinees were measured at 1∼4 months or 1 year after primary basic vaccination and a month, 1∼2 years after booster vaccination by indirect immunofluorescent assay (IFA), High density particle agglutination assay (HDPA), and plaque reduction neutralization test (PRNT). Results : Serconversion of twentyone vaccinees on 1∼4 months after primary vaccination were 20/21 (95.2%), 19/21 (90.5%) and 14/21 (66.7%) whose geometric mean antibody titers were 262,248,120; Forty vaccinees on one year after primary vaccination were 25/40 (62.5%), 18/40 (45.0%), 9/40 (22.5%) whose geometric mean antibody titers were 90,56,24 by IFA, HDPA, PRNT, respectively. Seroconversion of eight vaccinees on one month after booster vaccination were 11/12 (91.7%), 9/12 (75.0%) whose mean antibody titers were 296,33, and seven vaccinees on 3 months after second booster vaccination were 7/7 (100%), 6/7 (85.7%) whose mean antibody titers were 54,946 by IFA, PRNT, respectively. Conclusion : The boost vaccination is necessary at 12 months after primary basic vaccination of Hantavax™ for maintaining high level of antibodies against of Hantaan virus, and antibodies persist at least two years.