Modification of dengue virus strains by passage in primary dog kidney cells: Preparation of candidate vaccines and immunization of monkeys
Modification of dengue virus strains by passage in primary dog kidney cells: Preparation of candidate vaccines and immunization of monkeys
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DOI：
10.4269/ajtmh.2003.69.12
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发表时间：
2003-12-01
影响因子：
3.3
通讯作者：
Hoke, CH
中科院分区：
文献类型：
--
作者：
Eckels, KH;Dubois, DR;Hoke, CH
通过在原代犬肾（PDK）细胞培养物中传代，对四种DENY血清型中每种的登革（DENV）病毒株进行修饰，并在胎恒河猴二倍体细胞培养物中最终生产疫苗批次。将由连续传代的DENV组成的“毒株组”与每种毒株的未修饰的亲本病毒一起沿着接种在恒河猴中。通过测量病毒血症和免疫应答，将候选疫苗与未修饰的亲本病毒进行比较。除了一种DENV-1株外，所有DENV-1株在PDK细胞传代后在猴中的感染均减少。DENV-3毒株在PDK细胞传代后失去所有猴感染性。通过这一选择过程，选择了12种候选疫苗进行I期人体试验。
Dengue (DENV) virus strains for each of the four DENY serotypes were modified by passage in primary dog kidney (PDK) cell cultures with final manufacture of vaccine lots in fetal rhesus monkey diploid cell cultures. "Strain sets" consisting of serially-passaged DENV were inoculated in rhesus monkeys along with unmodified parent viruses for each strain. Vaccine candidates were compared with unmodified parent viruses by measuring viremia and immune responses. All except one DENV-1 strain demonstrated reduced infection in monkeys after PDK cell passage. A DENV-3 strain lost all monkey infectivity after PDK cell passage. Twelve vaccine candidates were selected for Phase I human trials through this selection process.