Putnak R, Barvir D A, Burrous J M, Dubois D R, D'Andrea V M, Hoke C H, Sadoff J C, Eckels K H
Walter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, Washington, DC 20307-5100, USA.
J Infect Dis. 1996 Dec;174(6):1176-84. doi: 10.1093/infdis/174.6.1176.
The feasibility of a purified, inactivated dengue (DEN) vaccine made in Vero cells was explored. A DEN-2 virus candidate was chosen for production of a monotypic, purified, inactivated vaccine (PIV). Virus was harvested from roller bottle culture supernatants, concentrated, and purified on sucrose gradients. The purified virus was inactivated with 0.05% formalin at 22 degrees C. After inactivation, the virus retained its antigenicity and was immunogenic in mice and rhesus monkeys, in which it elicited high titers of DEN-2 virus-neutralizing antibody. Mice were completely protected against challenge with live, virulent virus after receiving two 0.15-microg doses of PIV. Monkeys vaccinated with three doses ranging as low as 0.25 microg demonstrated complete absence or a significant reduction in the number of days of viremia after challenge with homologous virus. These results warrant further testing and development of PIVs for other DEN virus serotypes.
探讨了在Vero细胞中生产纯化灭活登革热(DEN)疫苗的可行性。选择了一种DEN - 2病毒候选株来生产单价、纯化、灭活疫苗(PIV)。病毒从滚瓶培养上清液中收获,经浓缩后在蔗糖梯度上进行纯化。纯化后的病毒在22℃下用0.05%福尔马林灭活。灭活后,病毒保留了其抗原性,并且在小鼠和恒河猴中具有免疫原性,在这些动物中它能诱导出高滴度的DEN - 2病毒中和抗体。小鼠在接受两剂0.15微克的PIV后,对活的强毒病毒攻击具有完全保护作用。接种三剂低至0.25微克疫苗的猴子在受到同源病毒攻击后,病毒血症天数完全没有或显著减少。这些结果保证了对其他DEN病毒血清型的PIV进行进一步测试和开发。