INTRANASAL IMMUNIZATION OF RHESUS MONKEY WITH ROTAVIRUS

虽然肠套叠的发生与肠道内轮状病毒复制之间的关系尚未确定，但唯一获得许可的轮状病毒疫苗(RotaShield)是一种口服减毒活疫苗，由于其可能与肠套叠有关，已被召回市场。由于很难在实验上解决这个问题，我们决定寻求另一种方法来开发安全有效的轮状病毒疫苗，该疫苗使用一种无效的或温度敏感的(TS)轮状病毒疫苗，该疫苗经鼻腔给药，从而绕过病毒在肠道内的复制。作为该项目的第一步，我们使用恒河猴和活的恒河猴轮状病毒(RRV)的同源系统来研究活的候选轮状病毒疫苗的致病性和免疫原性。用大约106pfu的RRV经鼻腔感染两只幼年恒河猴。这些动物没有表现出任何不良的临床症状。其中一只动物在粪便中排出RRV 7天，并在3周后产生血清反应。在攻击后的前3天从这种动物的鼻拭子中收集的RRV含量很低(8x101到5x102pfu/ml)。第二只动物在攻击后的头两天在粪便中排出RRV，没有产生血清反应。在攻击后的头两天，从该动物的鼻拭子中检测到低水平的RRV(~1×101pfu/ml)。目前正在检测动物血清中的IgA抗体水平。

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the only licensed rotavirus vaccine (RotaShield) which is a live attenuated vaccine delivered orally has been withdrawn from market because of its putative association with intussusception.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.