Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1.
Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1.
复制标题
DOI：
10.1016/j.vaccine.2010.02.051
复制
发表时间：
2010-04-19
期刊：
影响因子：
5.5
通讯作者：
Samal, Siba K.
中科院分区：
文献类型：
--
作者：
Khattar, Sunil K.;Collins, Peter L.;Samal, Siba K.
牛疱疹病毒1型（BHV-1）是引起牛呼吸道疾病的主要病原。对牛进行BHV-1疫苗接种是一个高度优先事项。目前改良的BHV-1活疫苗的一个主要问题是它们引起潜伏感染和随后再活化的能力，从而导致许多暴发。因此，有必要制定替代战略。我们从添加的基因中产生了两种表达BHV-1糖蛋白D（gD）的重组纽卡斯尔病病毒（NDV）。一种重组体rLaSota/gDFL表达gD而不进行任何修饰。另一个重组体rLaSota/gDF表达嵌合gD，其中gD的胞外域与NDV融合F糖蛋白的跨膜结构域和胞质尾融合。值得注意的是，由rLaSota/gDFL病毒表达的天然gD掺入NDV病毒粒子的效率是天然NDV蛋白的2.5倍，而嵌合gD即使在感染的细胞表面上大量表达也不能检测到掺入。gD基因的表达并没有增加rNDV载体在鸡体内的毒力。用重组NDV单次鼻内和鼻内接种小牛，引起对BHV-1特异性的粘膜和全身抗体，对rLaSota/gDFL的应答高于rLaSota/gDF。在用BHV-1攻击后，与空载体对照相比，用重组NDV免疫的小牛具有较低的滴度和较早的攻击病毒清除，并且用rLaSota/gDFL观察到疾病减少。攻毒后，与rNDV亲本病毒相比，用rNDV疫苗免疫的动物中BHV-1特异性血清抗体的滴度更高，表明疫苗引发了二次应答。我们的数据表明，NDV可用作牛的疫苗载体，BHV-1 gD可用于抗BHV-1感染的粘膜疫苗，但可能需要通过第二剂量或包含额外的BHV-1抗原来增强。
Bovine herpesvirus-1 (BHV-1) is a major cause of respiratory tract diseases in cattle. Vaccination of cattle against BHV-1 is a high priority. A major concern of currently modified live BHV-1 vaccines is their ability to cause latent infection and subsequent reactivation resulting in many outbreaks. Thus, there is a need for alternative strategies. We generated two recombinant Newcastle disease viruses (NDVs) expressing the glycoprotein D (gD) of BHV-1 from an added gene. One recombinant, rLaSota/gDFL, expressed gD without any modification. The other recombinant, rLaSota/gDF, expressed a chimeric gD in which the ectodomain of gD was fused with the transmembrane domain and cytoplasmic tail of the NDV fusion F glycoprotein. Remarkably, the native gD expressed by rLaSota/gDFL virus was incorporated into the NDV virion 2.5-fold more efficiently than the native NDV proteins, whereas the chimeric gD was not detectably incorporated even though it was abundantly expressed on the infected cell surface. The expression of gD did not increase the virulence of the rNDV vectors in chickens. A single intranasal and intratracheal inoculation of calves with either recombinant NDV elicited mucosal and systemic antibodies specific to BHV-1, with the responses to rLaSota/gDFL being higher than those to rLaSota/gDF. Following challenge with BHV-1, calves immunized with the recombinant NDVs had lower titers and earlier clearance of challenge virus compared to the empty vector control, and reduced disease was observed with rLaSota/gDFL. Following challenge, the titers of serum antibodies specific to BHV-1 were higher in the animals immunized with the rNDV vaccines compared to the rNDV parent virus, indicating that the vaccines primed for secondary responses. Our data suggest that NDV can be used as a vaccine vector in bovines and that BHV-1 gD may be useful in mucosal vaccine against BHV-1 infection, but might require augmentation by a second dose or the inclusion of additional BHV-1 antigens.
登录
查看更多内容
影响因子：
5.4
作者：
DiNapoli, Joshua M.;Yang, Lijuan;Bukreyev, Alexander
通讯作者：
Bukreyev, Alexander
影响因子：
5.4
作者：
Carnero, Elena;Li, Wenjing;Garcia-Sastre, Adolfo
通讯作者：
Garcia-Sastre, Adolfo
影响因子：
3.8
作者：
Gao, Y;Wang, C;Splitter, GA
通讯作者：
Splitter, GA
影响因子：
5.5
作者：
Filgueira, DMP;Zamorano, PI;Sadir, AM
通讯作者：
Sadir, AM
影响因子：
5.4
作者：
Bukreyev, A;Bukreyev, A;Sanchez, A
通讯作者：
Sanchez, A