포르말린 처리 쥐뇌조직유래 불활화 한탄바이러스 백신(한타박스R) 2회 접종 후 혈중 중화항체 생성에 관한 연구

Abstract

BACKGROUND: Hemorrhagic fever with renal syndrome is a serious health problem in Korea. Formalin inactivated mouse brain-derived Hantaan virus vaccine (HantavaxR) has been available since 1990 and recom-mended in national immunization programs for children and adults by the health authority. However, Hantavax has not been evaluated for efficacy in a randomized, placebo-controlled clinical trial and data on neutralizing antibody responses in human trials are limited. To investigate humoral immune responses to Hantavax, we studied volunteers immunized according to the recom-mended two dose schedule. METHODS: With informed consent, 30 healthy adults were immunized with two doses of Hantavax (Lot No. 6001, 2360002) 0.5ml given intramuscularly on deltoid muscle 4 weeks apart. The monovalent vaccine, pro-duced from the ROK 84-105 strain, is inactivated with 0.05% formalin and has an ELISA antigen titer of 4096. Sera were collected before vaccination and 4 weeks after each dose for a total of 90 serum samples from 30 vaccinees. Neutralizing antibodies were measured at Unit-ed States Army Medical Research Institute of Infectious Disease (Ft. Detrick, MD) in plaque reduction neutrali-zation tests. Antibody titers were expressed as the highest serum dilution that reduced the standard viral dose (45 ~ 58 plaque forming units of Hantaan virus strain 76-118 by 50 percent. Serum binding antibodies also were mea-sured in a high density particle agglutination test (Hanta-dia R) at Yonsei University. RESULTS: Neutralizing antibodies were detected in only 5 of 30 vaccinees given two doses of Hantavax, yielding seroconversion rate of 16.7%. The endpoint titers of reactive sera were 1:320, 1:10, 1:10, 1:10, and 1:40 respectively. The seroconversion rate measured by high density particle agglutination test was 80.0% (24/30). CONCLUSION: These results indicated that the poor neutralizing antibody response observed in this study suggests that further evaluations of the protective effi-cacy of inactivated mouse brain-derived Hantaan virus vaccine against HFRS.