Zhang Xiaorong, Bo Zongyi, Meng Chenchen, Chen Yin, Zhang Chengcheng, Cao Yongzhong, Wu Yantao
Jiangsu Co-Innovation Center for the Prevention and Control of Animal Infectious Disease and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Viruses. 2021 Aug 13;13(8):1606. doi: 10.3390/v13081606.
H9N2 avian influenza virus (AIV) has become endemic in many countries, causing great economic losses when co-infected with other pathogens. So far, several live vaccines based on Newcastle disease virus (NDV) vectors expressing influenza hemagglutinin (HA) have been developed. However, the thermostable recombinant NDV is rarely reported. In this study, using a thermostable NDV rAHR09 strain as the vector, three recombinant NDVs expressing native HA, chimeric HA ectodomain with transmembrane domain/C-terminal cytoplasmic tail domain from fusion protein of NDV, and HA ectodomain were generated, designated rAHR09-HA, rAHR09-HAF, and rAHR09-HAE. The MDT value of three recombinant NDVs was above 120 h, their ICPI value was about 0.03, and the recombinant NDVs were still infectious when treated for 100 min under 56 °C, which demonstrated that the recombinant NDVs kept the lentogenic and thermostable nature of rAHR09. The immunization data showed that rAHR09-HA and rAHR09-HAF induced a higher HI antibody titer against H9N2 AIV and NDV. After being challenged with H9N2 AIV, the rAHR09-HA and rAHR09-HAF could significantly reduce the virus shedding in cloacal and tracheal swab samples. Our results suggest that rAHR09-HA and rAHR09-HAF might be vaccine candidates against H9N2 AIV.
H9N2禽流感病毒（AIV）已在许多国家成为地方病，与其他病原体共同感染时会造成巨大经济损失。到目前为止，已经开发了几种基于表达流感血凝素（HA）的新城疫病毒（NDV）载体的活疫苗。然而，热稳定的重组NDV很少被报道。在本研究中，使用热稳定的NDV rAHR09株作为载体，构建了三种表达天然HA、带有来自NDV融合蛋白跨膜结构域/ C末端胞质尾结构域的嵌合HA胞外结构域以及HA胞外结构域的重组NDV，分别命名为rAHR09-HA、rAHR09-HAF和rAHR09-HAE。三种重组NDV的MDT值均高于120小时，ICPI值约为0.03，并且在56℃下处理100分钟后仍具有感染性，这表明重组NDV保持了rAHR09的弱毒株和热稳定特性。免疫数据显示，rAHR09-HA和rAHR09-HAF诱导产生了更高的针对H9N2 AIV和NDV的HI抗体效价。用H9N2 AIV攻击后，rAHR09-HA和rAHR09-HAF可显著减少泄殖腔和气管拭子样本中的病毒脱落。我们的结果表明，rAHR09-HA和rAHR09-HAF可能是抗H9N2 AIV的候选疫苗。
