Jang Hyesun, Ngunjiri John M, Lee Chang-Won
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, United States of America.
Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, United States of America.
PLoS One. 2016 Jun 3;11(6):e0156603. doi: 10.1371/journal.pone.0156603. eCollection 2016.
Influenza virus mutants that encode C-terminally truncated NS1 proteins (NS1-truncated mutants) are attractive candidates for avian live attenuated influenza vaccine (LAIV) development because they are both attenuated and immunogenic in chickens. We previously showed that a high protective efficacy of NS1-truncated LAIV in chickens corresponds with induction of high levels of type I interferon (IFN) responses in chicken embryonic fibroblast cells. In this study, we investigated the relationship between induction of IFN and IFN-stimulated gene responses in vivo and the immunogenicity and protective efficacy of NS1-truncated LAIV. Our data demonstrates that accelerated antibody induction and protective efficacy of NS1-truncated LAIV correlates well with upregulation of IFN-stimulated genes. Further, through oral administration of recombinant chicken IFN alpha in drinking water, we provide direct evidence that type I IFN can promote rapid induction of adaptive immune responses and protective efficacy of influenza vaccine in chickens.
编码C末端截短的NS1蛋白的流感病毒突变体（NS1截短突变体）是禽用减毒活流感疫苗（LAIV）开发的有吸引力的候选者，因为它们在鸡中既具有减毒作用又具有免疫原性。我们之前表明，NS1截短的LAIV在鸡中的高保护效力与鸡胚成纤维细胞中高水平的I型干扰素（IFN）反应的诱导相对应。在本研究中，我们调查了体内IFN诱导与IFN刺激基因反应之间的关系以及NS1截短的LAIV的免疫原性和保护效力。我们的数据表明，NS1截短的LAIV的加速抗体诱导和保护效力与IFN刺激基因的上调密切相关。此外，通过在饮用水中口服重组鸡IFNα，我们提供了直接证据，证明I型IFN可以促进鸡体内适应性免疫反应的快速诱导和流感疫苗的保护效力。
