Induction of protective immunity by topic application of a recombinant adenovirus expressing rabies virus glycoprotein
Induction of protective immunity by topic application of a recombinant adenovirus expressing rabies virus glycoprotein
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DOI：
10.1016/s0378-1135(01)00523-5
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发表时间：
2002-04-02
影响因子：
3.3
通讯作者：
Fu, ZF
中科院分区：
文献类型：
--
作者：
Lees, CY;Briggs, DJ;Fu, ZF
本研究的目的是确定通过非侵入性疫苗接种途径（通过局部应用）将表达狂犬病病毒糖蛋白（Adrab.gp）的复制缺陷型重组腺病毒接种到皮肤（NIVS）上是否可以引发免疫应答和/或针对狂犬病的保护。通过NIVS用各种剂量的Adrab.gp免疫小鼠组。为了比较，用Adrab.gp肌内、皮下或皮内免疫小鼠组。小鼠在第一次免疫后1个月和2个月接受两次加强免疫。在第一次和第二次免疫后第21天以及第三次免疫后第14天测量病毒中和抗体（VNA）滴度。用2 × 10（7）和2 × 10（8）pfu Adrab.gp疫苗NIVS免疫的小鼠中有50%产生VNA。而对照小鼠或用最低剂量（2 × 10（6）pfu）Adrab.gp病毒的NIVS免疫的小鼠均未产生VNA。然而.该低剂量在通过肠胃外途径免疫的小鼠中诱导高滴度的VNA。在最后一次免疫后两周，所有小鼠用致死剂量的狂犬病病毒进行攻击。用大于或等于2 x 10（7）pfu Adrab.gp病毒的NIVS免疫的动物中超过70%在攻击中存活，而阴性对照组和用最低剂量Adrab.gp的NIVS免疫的组中的所有小鼠死于狂犬病。综上所述，结果表明，具有Adrab.gp的NIVS可以诱导小鼠中VNA的产生和对狂犬病病毒致死性攻击的保护。(C)2002 Elsevier Science B. V.保留所有权利。
The objective of this study was to determine if a replication defective recombinant adenovirus expressing rabies virus glycoprotein (Adrab.gp) given through a non-invasive vaccination route (by topical application) onto the skin (NIVS) could elicit an immune response and/or protection against rabies. Groups of mice were immunized by NIVS with various doses of Adrab.gp. For comparison, groups of mice were immunized intramuscularly, subcutaneously, or intradermally with Adrab.gp. Mice received two booster immunizations at I and 2 months after the first immunization. Virus neutralizing antibody (VNA) titers were measured at day 21 after the first and second immunizations and at day 14 after the third immunization. Fifty percent of the mice immunized by NIVS with 2 x 10(7) and 2 x 10(8) pfu Adrab.gp vaccine developed VNA. whereas none of the control mice or the mice immunized by NIVS with the lowest dose (2 x 10(6) pfu) of Adrab.gp virus developed VNA. However. this low dose induced high titers of VNA in mice immunized by parenteral routes. Two weeks after the last immunization, all the mice were challenged with a lethal dose of rabies virus. More than 70% of the animals immunized by NIVS with greater than or equal to2 x 10(7) pfu Adrab.gp virus survived the challenge, whereas all the mice in the negative control group and the group immunized by NIVS with the lowest dose of Adrab.gp succumbed to rabies. Taken together, the results suggest that NIVS with Adrab.gp can induce VNA production and protection against lethal challenge with rabies virus in mice. (C) 2002 Elsevier Science B.V. All rights reserved.