An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys

被引:29
作者
Raengsakulrach, B
Nisalak, A
Gettayacamin, M
Thirawuth, V
Young, GD
Myint, KSA
Ferguson, LM
Hoke, CH
Innis, BL
Vaughn, DW
机构
[1] USAMC, Dept Virol, AFRIMS, Bangkok 10400, Thailand
[2] USAMC, Dept Vet Med, AFRIMS, Bangkok 10400, Thailand
[3] Pasteur Merieux Connaught, Swiftwater, PA 18370 USA
[4] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Virus Dis, Washington, DC 20307 USA
关键词
D O I
10.4269/ajtmh.1999.60.329
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Placebo-controlled field efficacy trials of new Japanese encephalitis (JE) vaccines may be impractical. Therefore, an animal model to evaluate efficacy of candidate JE vaccines is sought. Previous work has shown that exposure of monkeys to JE virus (JEV) via the intranasal route results in encephalitis. Here we report the further development of this model and the availability of titered virus stocks to assess the protective efficacy of JE vaccines. To determine the effective dose of our JE challenge virus, dilutions of a stock JEV (KE-93 isolate) were inoculated into four groups of three rhesus monkeys. A dose-dependent response was observed and the 50% effective dose (ED50) was determined to be 6.0 x 10(7) plaque forming units (pfu). Among animals that developed encephalitis, clinical signs occurred 9-14 days postinoculation. Infection with JEV was confirmed by detection of JEV in nervous tissues and IgM to JEV in the cerebrospinal fluid. Viremia with JEV was also detected intermittently throughout infection. Validation of the model was performed using a known effective JE vaccine and saline control. One ED90 of virus (2.0 x 10(9) pfu) was used as a challenge dose. Four of four animals that received saline control developed encephalitis while one of four monkeys administered the JE vaccine did so. This study demonstrates that the virus strain, route of inoculation, dose, and the outcome measure (encephalitis) are suitable for assessment of protective efficacy of candidate JE vaccines.
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页码:329 / 337
页数:9
相关论文
共 34 条
[1]   SIDE-EFFECTS WITH JAPANESE ENCEPHALITIS VACCINE [J].
ANDERSEN, MM ;
RONNE, T .
LANCET, 1991, 337 (8748) :1044-1044
[2]  
[Anonymous], VACCINES
[3]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[4]   TECHNIQUES FOR HEMAGGLUTINATION AND HEMAGGLUTINATION-INHIBITION WITH ARTHROPOD-BORNE VIRUSES [J].
CLARKE, DH ;
CASALS, J .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1958, 7 (05) :561-573
[5]   JAPANESE ENCEPHALITIS-VIRUS LIVE-ATTENUATED VACCINE, CHINESE STRAIN SA14-14-2 - ADAPTATION TO PRIMARY CANINE KIDNEY-CELL CULTURES AND PREPARATION OF A VACCINE FOR HUMAN USE [J].
ECKELS, KH ;
YONGXIN, Y ;
DUBOIS, DR ;
MARCHETTE, NJ ;
TRENT, DW ;
JOHNSON, AJ .
VACCINE, 1988, 6 (06) :513-518
[6]  
GHOSH SN, 1990, INDIAN J MED RES-A, V91, P408
[7]   INTRANASAL INFECTION OF MONKEYS WITH JAPANESE ENCEPHALITIS-VIRUS - CLINICAL RESPONSE AND TREATMENT WITH A NUCLEASE-RESISTANT DERIVATIVE OF POLY(I).POLY(C) [J].
HARRINGTON, DG ;
HILMAS, DE ;
ELWELL, MR ;
WHITMIRE, RE ;
STEPHEN, EL .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1977, 26 (06) :1191-1198
[8]   PROTECTION AGAINST JAPANESE ENCEPHALITIS BY INACTIVATED VACCINES [J].
HOKE, CH ;
NISALAK, A ;
SANGAWHIPA, N ;
JATANASEN, S ;
LAORAKAPONGSE, T ;
INNIS, BL ;
KOTCHASENEE, SO ;
GINGRICH, JB ;
LATENDRESSE, J ;
FUKAI, K ;
BURKE, DS .
NEW ENGLAND JOURNAL OF MEDICINE, 1988, 319 (10) :608-614
[9]  
HOMIN L, 1986, VIRUS VACCINES ASIAN, P159
[10]  
IMAM IZE, 1957, J IMMUNOL, V79, P253