INTRANASAL IMMUNIZATION OF RHESUS MONKEY WITH ROTAVIRUS

恒河猴轮状病毒鼻内免疫

• 批准号: 6414663
• 负责人: Yasutaka Hoshino
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/6414663
• 关键词: Macaca mulatta; Rotavirus; active immunization; antiviral antibody; immunoglobulin A; inhalation drug administration; microorganism culture; nonhuman therapy evaluation; rotavirus vaccines; temperature sensitive mutant; vaccine development

Although the association between an occurrence of intussusception and rotavirus replication in the gut has not been established, the only licensed rotavirus vaccine (RotaShield) which is a live attenuated vaccine delivered orally has been withdrawn from market because of its putative association with intussusception. Since it is difficult to solve this problem experimentally, we decided to seek an alternative approach to the development of a safe and effective rotavirus vaccine employing a non-viable or temperature sensitive (ts) rotavirus vaccine which is administered intranasally and thus bypassing virus replication in the gut. As a first step of the project, we studied pathogenicity and immunogenicity of a live candidate rotavirus vaccine by using a homologous system of rhesus monkeys and live rhesus monkey rotavirus (RRV). Two juvenile rhesus monkeys were infected intranasally with approximately 106 PFU of RRV. The animals did not show any adverse clinical signs. One animal shed RRV in stools for 7 days and developed a seroresponse 3 weeks later. Nasal swabs collected from this animal during the first 3 days post-challenge contained low levels (8 x 101 to 5 x 102 PFU/ml) of RRV. The second animal shed RRV in stools during the first two days post-challenge and did not develop a seroresponse. Low levels (~ 1 x 101 PFU/ml) of RRV were detected in nasal swabs obtained from this animal during the first two days post-challenge. Levels of serum IgA antibodies in animals are being examined.

虽然肠套叠的发生与肠道内轮状病毒复制之间的关联尚未确定，但唯一获得许可的口服轮状病毒减毒活疫苗（rotasshield）已退出市场，因为它被认为与肠套叠有关。由于很难通过实验解决这一问题，我们决定寻找一种替代方法来开发安全有效的轮状病毒疫苗，采用非活的或温度敏感的（ts）轮状病毒疫苗，通过鼻内给药，从而绕过病毒在肠道中的复制。作为该项目的第一步，我们利用恒河猴和活恒河猴轮状病毒（RRV）的同源系统，研究了一种候选轮状病毒活疫苗的致病性和免疫原性。两只幼年恒河猴鼻内感染了大约106 PFU的RRV。实验动物未出现任何不良临床症状。一只动物在粪便中排出RRV 7天，3周后出现血清反应。在攻击后头3天从该动物收集的鼻拭子含有低水平的RRV （8 × 101至5 × 102 PFU/ml）。第二只动物在感染后的头两天通过粪便排出RRV，没有产生血清反应。在攻击后头两天从该动物获得的鼻拭子中检测到低水平（~ 1 × 101 PFU/ml）的RRV。正在检查动物血清中IgA抗体的水平。