Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo.
Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo.
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DOI：
10.1128/jvi.01473-18
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发表时间：
2018-12-01
影响因子：
5.4
通讯作者：
Vervelde L
中科院分区：
文献类型：
--
作者：
Ellis S;Keep S;Britton P;de Wit S;Bickerton E;Vervelde L
传染性支气管炎病毒引起急性、高度传染性的呼吸道疾病，对家禽业造成重大经济损失。表面蛋白，刺突（S），特别是S1亚基的氨基酸差异与交叉保护作用差有关。现有的疫苗提供较差的交叉保护，基于无致病性BeauR的合理设计的减毒活疫苗可以解决这些问题。为了确定S1在保护中的作用，进行了一系列rIBV同源疫苗接种试验。用嵌合rIBV单次接种诱导病毒特异性部分保护性免疫，其特征在于病毒载量和血清抗体滴度的降低。然而，BeauR-M41（S）是唯一一种提高针对临床体征和气管纤毛活性丧失的保护水平的疫苗接种。生长特性表明，所有的rIBV在体外复制到相似的水平。加强疫苗接种和具有改善的体内复制的rIBV可以提高保护水平。基于单一病毒血清型的针对传染性支气管炎病毒（IBV）的疫苗接种方案通常诱导针对血清型的不充分水平的交叉保护，并且使用两种或更多种抗原多样性疫苗以试图提供更广泛的保护。表面蛋白，刺突（S），特别是S1亚基的氨基酸差异与交叉保护作用差有关。在这里，同源疫苗接种试验与重组IBV（rIBV）的基础上的非致病性菌株，BeauR，进行阐明的作用，S1的保护。用表达强毒株M41或QX的S1的rIBV，BeauR-M41（S1）和BeauR-QX（S1），对无特异性病原体的鸡进行单次接种，根据纤毛活性和临床体征，对同源攻击产生不完全保护。如果异源S1和S2连接，则加标可能存在构象问题，表明同源S2可能是必需的。为了解决这一问题，进行了一项同源疫苗接种-攻击试验，该试验掺入了表达来自M41、BeauR-M41（S）的全刺突和来自M41、BeauR-M41（S2）的S2亚基的rIBV。所有嵌合病毒在体外生长至相似滴度，诱导病毒特异性部分保护性免疫，通过细胞浸润、气管和结膜中病毒RNA载量的减少以及更高的血清抗IBV滴度来证明。总的来说，这些发现表明，用rIBV接种疫苗使禽类准备好进行攻击，但病毒从头部的粘膜组织中迅速清除。基于纤毛活性和临床体征，嵌合S1和S2病毒的保护效果不如BeauR-M41（S）。加强疫苗接种和具有改善的体内复制的rIBV可以提高保护水平。重要性传染性支气管炎病毒引起急性、高度传染性呼吸道疾病，对家禽业造成重大经济损失。表面蛋白，刺突（S），特别是S1亚基的氨基酸差异与交叉保护作用差有关。现有的疫苗提供较差的交叉保护，基于无致病性BeauR的合理设计的减毒活疫苗可以解决这些问题。为了确定S1在保护中的作用，进行了一系列rIBV同源疫苗接种试验。用嵌合rIBV单次接种诱导病毒特异性部分保护性免疫，其特征在于病毒载量和血清抗体滴度的降低。然而，BeauR-M41（S）是唯一一种提高针对临床体征和气管纤毛活性丧失的保护水平的疫苗接种。生长特性表明，所有的rIBV在体外复制到相似的水平。加强疫苗接种和具有改善的体内复制的rIBV可以提高保护水平。
Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection. Vaccination regimes against Infectious bronchitis virus (IBV), which are based on a single virus serotype, often induce insufficient levels of cross-protection against serotypes and two or more antigenically diverse vaccines are used in attempt to provide broader protection. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, are associated with poor cross-protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs), based on the apathogenic strain, BeauR, were conducted to elucidate the role of S1 in protection. A single vaccination of specific-pathogen-free chickens with rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1), gave incomplete protection against homologous challenge, based on ciliary activity and clinical signs. There could be conformational issues with the spike if heterologous S1 and S2 are linked, suggesting a homologous S2 might be essential. To address this, a homologous vaccination-challenge trial incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar titers in vitro, induced virus-specific partial protective immunity, evident by cellular infiltrations, reductions in viral RNA load in the trachea and conjunctiva and higher serum anti-IBV titers. Collectively, these findings show that vaccination with rIBVs primed the birds for challenge but the viruses were cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses did not protect as effectively as BeauR-M41(S) based on ciliary activity and clinical signs. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection. IMPORTANCE Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.