Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs

Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs
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DOI:
10.1016/j.virol.2012.06.001
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发表时间:
2012-10-25
期刊:
影响因子:
3.7
通讯作者:
Bu, Zhigao
Bu, Zhigao
中科院分区:
医学3区
文献类型:
--
作者:
Kong, Dongni;Wen, Zhiyuan;Bu, Zhigao

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尼帕病毒(Nipah Virus,NIV)属于副粘病毒科,可引起人类致死性脑炎,给养猪业造成巨大的经济损失。在这里,我们构建了分别表达新城疫病毒G蛋白和F蛋白的重组新城疫强毒LaSota株(命名为RLA-NiVG和RLA-NiVF),并评价了它们在小鼠和猪身上的免疫原性。RLA-NiVG和RLA-NiVF在鸡蛋中表现出与LaSota病毒相似的生长特性。RLA-NiVG和RLA-NiVF的混合感染可导致显著的合胞体形成,而在小鼠脑内联合接种这些病毒表明它们在至少一个哺乳动物物种中是安全的。动物免疫研究表明,RLA-NiVG和RLA-NiVF能诱导小鼠和猪产生Niv中和抗体反应,并能诱导小鼠产生F蛋白特异性CD8+T细胞反应。最重要的是,RLA-NiVG和RLA-NiVF单独或联合使用,可在猪体内诱导持久的中和抗体反应。因此,重组RLA-NiVG/F似乎很有希望成为猪和潜在的人类的新城疫疫苗候选。(C)2012 Elsevier Inc.保留所有权利。
Nipah virus (NiV), a member of the Paramyxoviridae family, causes deadly encephalitis in humans and huge economic losses to the pig industry. Here, we generated recombinant avirulent Newcastle disease virus (NDV) LaSota strains expressing the NiV G and F proteins respectively (designated as rLa-NiVG and rLa-NiVF), and evaluated their immunogenicity in mice and pigs. Both rLa-NiVG and rLa-NiVF displayed growth properties similar to those of LaSota virus in chicken eggs. Co-infection of rLa-NiVG and rLa-NiVF caused marked syncytia formation, while intracerebral co-inoculation of these viruses in mice showed they were safe in at least one mammalian species. Animal immunization studies showed rLa-NiVG and rLa-NiVF induced NiV neutralizing antibody responses in mice and pigs, and F protein-specific CD8+ T cell responses in mice. Most importantly, rLa-NiVG and rLa-NiVF administered alone or together, induced a long-lasting neutralizing antibody response in pigs. Recombinant rLa-NiVG/F thus appear to be promising NiV vaccine candidates for pigs and potentially humans. (C) 2012 Elsevier Inc. All rights reserved.