Recombinant infectious bronchitis coronavirus Beaudette with the spike protein gene of the pathogenic M41 strain remains attenuated but induces protective immunity
Recombinant infectious bronchitis coronavirus Beaudette with the spike protein gene of the pathogenic M41 strain remains attenuated but induces protective immunity
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DOI：
10.1128/jvi.78.24.13804-13811.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Cavanagh, D
中科院分区：
文献类型：
--
作者：
Hodgson, T;Casais, R;Cavanagh, D
我们将鸡传染性支气管炎冠状病毒（IBV）Beaudette株（Beau-R;对鸡无致病性）S蛋白的胞外域替换为致病性M41株的S蛋白，制备了重组IBV BeauR-M41（S）。我们以前已经表明，这改变了病毒在体外的向性（R。卡赛，B。Dove，D. Cavanagh和P.布里顿，J. Virol. 77：9084-9089，2003）。在此，我们评估了BeauR-M41（S）的致病性和免疫原性。重组BeauR-M41（S）和其非致病亲本Beau-R（基于气管中的snicking、鼻涕、喘息、流泪、罗音和纤毛停滞）之间的致病性没有一致的差异，并且与M41相比，两者在气管和鼻中的复制都很差;来自致病M41的S蛋白没有改变Beau-R的非致病性。Beau-R和BeauR-M41（S）均诱导了针对M41攻击的保护作用，如通过攻击病毒和鼻渗出物的恢复的不存在所评估的。在切断和纤毛抑制方面，BeauR-M41（S）诱导的保护作用（9只鸡中有7只[77%];通过纤毛抑制评估）大于Beau-R（9只鸡中有1只; 11%），但小于M41（100%）。BeauR-M41（S）诱导的对M41的更大保护可能与Beau-R的刺突蛋白的胞外结构域与M41的刺突蛋白的胞外结构域相差4.1%有关; S蛋白上的少量表位可能在诱导免疫中起不成比例的作用。这一结果为S基因交换在IBV疫苗研制中的应用提供了新的思路。
We have replaced the ectodomain of the spike (S) protein of the Beaudette strain (Beau-R; apathogenic for Gallus domesticus chickens) of avian infectious bronchitis coronavirus (IBV) with that from the pathogenic M41 strain to produce recombinant IBV BeauR-M41(S). We have previously shown that this changed the tropism of the virus in vitro (R. Casais, B. Dove, D. Cavanagh, and P. Britton, J. Virol. 77:9084-9089, 2003). Herein we have assessed the pathogenicity and immunogenicity of BeauR-M41(S). There were no consistent differences in pathogenicity between the recombinant BeauR-M41(S) and its apathogenic parent Beau-R (based on snicking, nasal discharge, wheezing, watery eyes, rales, and ciliostasis in trachea), and both replicated poorly in trachea and nose compared to M41; the S protein from the pathogenic M41 had not altered the apathogenic nature of Beau-R. Both Beau-R and BeauR-M41(S) induced protection against challenge with M41 as assessed by absence of recovery of challenge virus and nasal exudate. With regard to snicking and ciliostasis, BeauR-M41(S) induced greater protection (seven out of nine chicks [77%]; assessed by cilliostasis) than Beau-R (one out of nine; 11%) but less than M41 (100%). The greater protection induced by BeauR-M41(S) against M41 may be related to the ectodomain of the spike protein of Beau-R differing from that of M41 by 4.1%; a small number of epitopes on the S protein may play a disproportionate role in the induction of immunity. The results are promising for the prospects of S-gene exchange for IBV vaccine development.