STABILIZATION OF ORAL POLIOVIRUS VACCINE INFECTIVITY TO LYOPHILIZATION

口服脊髓灰质炎病毒疫苗冻干感染性的稳定

• 批准号: 2336433
• 负责人: R E LUNDQUIST
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2336433
• 关键词: capsid; chemical stability; crosslink; deuterium oxide; enzyme linked immunosorbent assay; lyophilization; oral administration; plaque assay; poliomyelitis vaccine; thermostability; virion; virulence; virus antigen

Oral poliovirus vaccine (OPV) rapidly loses infectivity and potency unless stored in a frozen state. Delivery of this vaccine would be greatly enhanced by the development of less stringent OPV storage conditions. Various laboratories throughout the world are attempting to stabilize the vaccine either by the addition of stabilizing compounds or the development of successful lyophilization procedures. We have sought to develop a lyophilization procedure for poliovirus. In contrast to some viral vaccines, poliovirus infectivity is severely diminished after lyophilization. We have evaluated different lyophilization conditions in conjunction with the addition of various substances prior to lyophilization in an attempt to devise a successful approach for poliovirus. Viral stability is assessed by an ELISA test for D-antigen and a plaque assay for infectivity. Inclusion of a lipid based reagent dramatically increases virus survival, by a factor of 1000x, resulting in 20-40% survival of infectivity after lyophilization. Further studies have raised the recovery of infectious virus to greater than 50% However, temperature stability studies have indicated that the lyophilized virus is not significantly different than virus in solution. Current efforts have focused on using procedures that stabilize the capsid architecture of the virion without impairing the infectivity of the virus. The use of cleavable bifunctional protein cross linkers has shown promise. However, the use of deuterium oxide appears to be a simpler and more acceptable approach. Therefore, we are winding up this project.

口服脊髓灰质炎病毒疫苗（OPV）迅速失去感染性和效力 除非在冷冻状态下储存。这种疫苗的交付将是 通过开发不太严格的OPV储存， 条件 世界各地的各种实验室都在试图 通过添加稳定化合物或通过添加稳定化合物来稳定疫苗， 开发成功的冻干程序。我们寻求 开发脊髓灰质炎病毒的冻干程序。 相比 一些病毒疫苗，脊髓灰质炎病毒的感染性严重减弱后， 冷冻干燥 我们已经评估了不同的冻干条件 在加入各种物质之前， 冷冻干燥，试图设计一种成功的方法， 脊髓灰质炎病毒。 通过ELISA检测D抗原评估病毒稳定性 和感染性噬菌斑检测。 包含基于脂质的试剂 大大增加病毒的存活率，增加了1000倍， 冻干后感染性存活率为20-40%。 进一步研究 将传染性病毒的回收率提高到50%以上， 然而，温度稳定性研究表明， 冻干的病毒与溶液中的病毒没有显著不同。 目前的努力集中在使用程序，稳定 病毒体的衣壳结构，而不损害 病毒 可裂解的双功能蛋白质交联剂的使用具有 显示承诺。 然而，氧化氘的使用似乎是一种 更简单和更容易接受的方法。 因此，我们要结束这场 项目

项目成果

High branched-chain alpha-keto acid intake, branched-chain alpha-keto acid dehydrogenase activity, and plasma and brain amino acid and plasma keto acid concentrations in rats.

• DOI: 10.1093/ajcn/52.2.313
• 发表时间: 1990-08
• 期刊: The American journal of clinical nutrition
• 作者: P L Crowell;K. P. Block;J J Repa-J;N. Torres;M D Nawabi;M G Buse;A. E. Harper