Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs
Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs
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DOI：
10.1016/j.vaccine.2011.10.098
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发表时间：
2012-01-05
期刊：
影响因子：
5.5
通讯作者：
Kehrli, Marcus E., Jr.
中科院分区：
文献类型：
--
作者：
Kappes, Matthew A.;Sandbulte, Matthew R.;Kehrli, Marcus E., Jr.
当代猪流感病毒（SIV）毒株的多样性阻碍了猪群的有效免疫。粘膜递送的减毒病毒疫苗是一种有可能提供广泛交叉保护的方法。反向遗传学衍生的带有截短 NS1 (NS1 Delta 126 TX98) 的 H3N2 SIV 病毒在幼猪鼻内递送时具有减毒作用并具有免疫原性。我们分析了断奶仔猪鼻内接种 NS1 Delta 126 TX98 与野生型 TX98 后的 T 细胞启动和交叉保护功效。与野生型病毒相比，截短突变体的体内复制是最小的。在体外再刺激试验中，感染野生型病毒的猪的 T 细胞反应幅度更大。根据激活标记 CD25 的表达，NS1 Delta 126 TX98 感染猪的外周 T 细胞回忆反应最小。然而，细胞内IFN-γ数据表明，减毒病毒在28天内诱导了病毒特异性CD4(+)CD8(-)、CD4(+)CD8(+)、CD4(-)CD8(+)和gamma delta T细胞。 IFN-γ反应似乎收缩，因为在攻击前的较晚时间点反应减少。异亚型 H1N1 攻击后 5 天（总共第 70 天）分离的 CD4(+)CD8(+) 细胞显示出对病毒再刺激的 CD25 反应升高。先前感染野生型 TX98 的猪可免受 H1N1 攻击病毒的复制。接种 NS1 Delta 126 TX98 疫苗与受感染肺部的 Th1 相关细胞因子水平显着降低相关，但提供了针对 H1N1 攻击的部分交叉保护。这些结果表明 NS1 Delta SIV 疫苗可以引发细胞介导的针对抗原不同菌株的交叉保护。由爱思唯尔有限公司出版
The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1 Delta 126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1 Delta 126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1 Delta 126 TX98 infected pigs were minimal. However, intracellular IFN-gamma data indicate that the attenuated virus induced virus-specific CD4(+)CD8(-), CD4(+)CD8(+), CD4(-)CD8(+), and gamma delta T cells within 28 days. The IFN-gamma response appeared to contract, as responses were reduced at later time points prior to challenge. CD4(+)CD8(+) cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1 Delta 126 TX98 was associated with significantly lower levels of Th1-associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1 Delta SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains. Published by Elsevier Ltd.