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新城疫-禽流感二价载体疫苗在商品鸡中的研发与评价。

Development and evaluation of Newcastle disease - avian influenza bivalent vector vaccines in commercial chickens.

机构信息

Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.

Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Research Center of Genetic Engineering of Pharmaceuticals of Heilongjiang Province, Northeast Agricultural University, Harbin, China; Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, China.

出版信息

Int Immunopharmacol. 2023 Jul;120:110363. doi: 10.1016/j.intimp.2023.110363. Epub 2023 May 26.

Abstract

Avian influenza (AI) and Newcastle disease (ND) are regarded as the leading viral infectious diseases affecting the global poultry industry. Vaccination is a successful therapeutic intervention to safeguard birds against both ND and AI infections. In this research, ND-AI bivalent vaccines were developed through the incorporation of HA and IRES-GMCSF gene fragments at varying locations of NDV rClone30 vectors. The two constructed vaccines were rClone30-HA-IRES-GMCSF(PM) and rClone30-HA(PM)-IRES-GMCSF(NP). Next, 27-day-old Luhua chickens (the maternal antibody level was reduced to 1.4 log2) were inoculated with the same dose of the vaccines, and humoral and cellular immune responses were assessed at multiple time points. Compared to the commercial vaccine, the levels of anti-NDV antibodies following the administration of the ND-AI vaccines were above the theoretical protection value of 4 log2. The levels of anti-AIV antibodies in the bivalent vaccine group were notably higher than those in the commercial vaccine group. Furthermore, the content of inflammatory factors and transcription levels were significantly increased in chickens administered ND-AI vaccines. The ND-AI vaccines induced stronger proliferative responses of B cells or CD3+, CD8+, and CD4 + T cells. Hematoxylin and eosin staining showed that the tissue damage induced by the two recombinant vaccines was similar to that of commercial vaccines. The outcomes of the study suggest that the two bivalent ND-AI vaccine candidates produced using the reverse genetics approach are both secure and effective. This approach not only enables the multiuse of one vaccine but also provides a new concept for the development of other vaccines against infectious viral diseases.

摘要

禽流感(AI)和新城疫(ND)被认为是影响全球家禽业的主要病毒性传染病。疫苗接种是保护鸟类免受 ND 和 AI 感染的成功治疗干预措施。在这项研究中,通过将 HA 和 IRES-GMCSF 基因片段插入到 NDV rClone30 载体的不同位置,开发了 ND-AI 二价疫苗。这两种构建的疫苗分别为 rClone30-HA-IRES-GMCSF(PM)和 rClone30-HA(PM)-IRES-GMCSF(NP)。接下来,将 27 日龄芦花鸡(母源抗体水平降至 1.4 log2)用相同剂量的疫苗接种,并在多个时间点评估体液和细胞免疫反应。与商业疫苗相比,ND-AI 疫苗接种后抗 NDV 抗体的水平高于 4 log2 的理论保护值。二价疫苗组的抗 AIV 抗体水平明显高于商业疫苗组。此外,接种 ND-AI 疫苗的鸡的炎症因子含量和转录水平显著增加。ND-AI 疫苗诱导更强的 B 细胞或 CD3+、CD8+和 CD4+T 细胞的增殖反应。苏木精和伊红染色显示,两种重组疫苗引起的组织损伤与商业疫苗相似。研究结果表明,使用反向遗传学方法生产的两种二价 ND-AI 疫苗候选物均安全有效。这种方法不仅可以实现一种疫苗的多用性,还为开发针对其他传染性病毒疾病的疫苗提供了新的概念。

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