Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus.
Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus.
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DOI：
10.3390/vaccines8030346
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发表时间：
2020-06-29
期刊：
影响因子：
7.8
通讯作者：
Ortego J
中科院分区：
文献类型：
--
作者：
Utrilla-Trigo S;Jiménez-Cabello L;Alonso-Ravelo R;Calvo-Pinilla E;Marín-López A;Moreno S;Lorenzo G;Benavides J;Gilbert S;Nogales A;Ortego J
蓝舌病病毒（BTV）的非结构蛋白NS 1（non-structural protein NS 1）含有免疫显性的CD 8 + T细胞表位，其序列在BTV血清型中高度保守，因此已成为开发通用BTV疫苗的主要工具。在这项工作中，我们已经工程多血清型BTV疫苗候选人的基础上重组黑猩猩腺病毒（ChAdOx 1）和修改的牛痘病毒安卡拉（MVA）载体表达的NS 1蛋白的BTV-4或其截短的形式NS 1-Nt。单剂量的ChAdOx 1-NS 1或ChAdOx 1-NS 1-Nt诱导了中度的CD 8 + T细胞应答，并保护IFNAR（-/-）小鼠免受致死剂量的BTV-4/MOR 09（BTV-1和BTV-4之间的一种抗性株）的攻击，尽管动物在感染后显示出低病毒血症。此外，用单剂量ChAdOx 1-NS 1免疫的IFNAR（-/-）小鼠在用致死剂量的BTV-8攻击后在没有病毒血症或临床体征的情况下受到保护。此外，表达NS 1或NS 1-Nt的异源初免-加强ChAdOx 1/MVA引发了强烈的NS 1特异性CD 8 + T细胞应答，并保护动物免受BTV-4/M0 R 09的侵害，甚至在免疫后16周，在攻击后的任何时间都检测不到病毒血症水平。在此基础上，对ChAdOx 1/MVA-NS 1的最佳免疫策略进行了绵羊免疫试验。未免疫的动物在感染后出现发热和病毒血症水平高达104 PFU/mL。相反，虽然在免疫绵羊中检测到病毒血症，但在没有临床体征的情况下，血液中的病毒水平比未免疫动物低100倍。
The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 104 PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs.
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影响因子：
3.7
作者：
Calvo-Pinilla E;Navasa N;Anguita J;Ortego J
通讯作者：
Ortego J
DOI：
10.1016/0147-9571(94)90044-2
发表时间：
1994-08-01
影响因子：
2
作者：
GIBBS, EPJ;GREINER, EC
通讯作者：
GREINER, EC
影响因子：
9.8
作者：
Leta, Samson;Fetene, Eyerusalem;Revie, Crawford W.
通讯作者：
Revie, Crawford W.
影响因子：
1.8
作者：
ANDREW, M;WHITELEY, P;COUPAR, B
通讯作者：
COUPAR, B
影响因子：
5.5
作者：
Alharbi NK;Padron-Regalado E;Thompson CP;Kupke A;Wells D;Sloan MA;Grehan K;Temperton N;Lambe T;Warimwe G;Becker S;Hill AVS;Gilbert SC
通讯作者：
Gilbert SC