College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
Vet Microbiol. 2024 Nov;298:110264. doi: 10.1016/j.vetmic.2024.110264. Epub 2024 Oct 9.
The H9N2 inactivated avian influenza vaccine cannot induce cellular and mucosal immune responses, while the attenuated Salmonella vector as an intracellular bacterium can induce dominant cellular and mucosal immune responses. However, it provides low protection against the virus when delivering viral antigens and needs further optimization. Chicken C-C motif chemokine ligand 5 (chCCL5) is an important CC chemokine associated with immune cell chemotaxis, migration, and viral infection. This study connected the sequence of chCCL5 (CCL5) with the hemagglutinin sequence of the H9N2 avian influenza virus (yH9HA), utilizing the attenuated Salmonella typhimurium vector containing the delayed lysis system MazE/F regulated by arabinose as a carrier. A vaccine strain of recombinant attenuated Salmonella typhimurium and H9N2 avian influenza virus HA, rSC0130 (pS0017-yH9HA-CCL5), was successfully constructed. The experimental results indicate that yH9HA-CCL5 can be expressed in 293 T cells; compared to the strain without CCL5, rSC0130 (pS0017-yH9HA-CCL5) can induce significantly increased cellular immune responses and provide better protective effects in H9N2 virus challenge experiments. The above results indicate that chCCL5 can significantly enhance the protective effect of Salmonella delivering H9N2 avian influenza virus HA protein vaccine against H9N2 avian influenza virus infection, providing valuable theoretical support for further improving the protective efficiency of recombinant attenuated Salmonella vectors for delivering viral antigens.
H9N2 灭活禽流感疫苗不能诱导细胞和黏膜免疫应答，而减毒沙门氏菌载体作为胞内细菌可以诱导优势的细胞和黏膜免疫应答。然而，当传递病毒抗原时，它提供的保护作用较低，需要进一步优化。鸡 C-C 基序趋化因子配体 5（chCCL5）是一种与免疫细胞趋化、迁移和病毒感染相关的重要 CC 趋化因子。本研究将 chCCL5（CCL5）的序列与 H9N2 禽流感病毒（yH9HA）的血凝素序列连接起来，利用含有阿拉伯糖调节的延迟裂解系统 MazE/F 的减毒鼠伤寒沙门氏菌载体作为载体。成功构建了重组减毒鼠伤寒沙门氏菌和 H9N2 禽流感病毒 HA 的疫苗株 rSC0130（pS0017-yH9HA-CCL5）。实验结果表明，yH9HA-CCL5 可在 293T 细胞中表达；与不含 CCL5 的菌株相比，rSC0130（pS0017-yH9HA-CCL5）可诱导显著增强的细胞免疫应答，并在 H9N2 病毒攻毒实验中提供更好的保护效果。上述结果表明，chCCL5 可显著增强沙门氏菌传递 H9N2 禽流感病毒 HA 蛋白疫苗对 H9N2 禽流感病毒感染的保护作用，为进一步提高重组减毒沙门氏菌载体传递病毒抗原的保护效率提供了有价值的理论支持。
