从禽类黏膜免疫系统洞悉禽流感黏膜疫苗研发策略

doi:10.13560/j.cnki.biotech.bull.1985.2025-0956

摘要/Abstract

摘要：

禽类黏膜免疫系统的特征包括弥散性淋巴组织、免疫球蛋白Y（IgY）介导的体液免疫、鸡黑色素瘤分化相关基因5（MDA5）依赖的天然免疫通路以及归巢与黏膜免疫共同体系。目前，传统灭活疫苗难以有效阻断禽流感病毒（AIV）的黏膜感染。相比之下，黏膜疫苗通过激发局部黏膜免疫，展现出显著优势。研究表明，基于反向遗传学优化的rClone30载体活疫苗可在免疫后第7天诱导新城疫病毒（NDV）与AIV抗体效价超过4 log₂的保护阈值，且抗体持续时间与细胞免疫反应强度均优于商品化灭活苗。此外，冷适应减毒活疫苗、重组乳酸菌疫苗、黏膜DNA疫苗与灭活苗的联合策略以及壳聚糖纳米颗粒递送的mRNA疫苗等不同技术平台，均能诱导高水平的特异性抗体和黏膜sIgA，并有效激活CD4⁺与CD8⁺ T细胞应答。这些免疫反应在攻毒实验中可将口咽拭子病毒阳性率从100%降至50%，实现100%的保护率，并显著减少病毒排出及减轻肺部病变。本文综述了禽类黏膜免疫系统的组织与功能机制，重点探讨了呼吸道黏膜免疫，并分析了当前禽流感黏膜疫苗的研发进展、应用现状与挑战。未来防控的关键在于深入解析黏膜免疫机制、优化疫苗设计与递送，以推动高效广谱黏膜疫苗的临床转化。

关键词: 禽黏膜免疫, 鸡呼吸道系统, 禽流感病毒, 黏膜疫苗

Abstract:

The features of the avian mucosal immune system include diffuse lymphoid tissues, humoral immunity mediated by immunoglobulin Y (IgY), innate immune signaling pathways dependent on chicken melanoma differentiation-associated gene 5 (MDA5), as well as a common homing and mucosal immune system. Currently, traditional inactivated vaccines are ineffective in blocking mucosal infection by avian influenza virus (AIV). In contrast, mucosal vaccines demonstrate significant advantages by eliciting local mucosal immunity. Studies have shown that live vaccines based on reverse genetics-optimized rClone30 vectors can induce antibody titers against Newcastle disease virus (NDV) and AIV exceeding the protective threshold of 4 log₂ by day 7 post-immunization, with both antibody persistence and the intensity of cellular immune responses surpassing those of commercial inactivated vaccines. Furthermore, various technological platforms—including cold-adapted attenuated live vaccines, recombinant lactobacillus vaccines, combined strategies of mucosal DNA vaccines and inactivated vaccines, and chitosan nanoparticle-delivered mRNA vaccines—can all induce high levels of specific antibodies and mucosal sIgA, and effectively activate CD4⁺ and CD8⁺ T-cell responses. In challenge experiments, these immune responses reduced the positive rate of oropharyngeal swab virus detection from 100% to 50%, achieved 100% protection, and significantly decreased viral shedding and lung lesions. This article reviews the organization and functional mechanisms of the avian mucosal immune system, with a focus on respiratory mucosal immunity, and analyzes the current progress, application status, and challenges in the development of avian influenza mucosal vaccines. The key to future prevention and control lies in deepening the understanding of mucosal immune mechanisms and optimizing vaccine design and delivery to promote the clinical translation of highly effective and broad-spectrum mucosal vaccines.

Key words: avian mucosal immune, chicken respiratory system, avian influenza virus, mucosal vaccine

朱美微, 张建峰, 王佳敏, 廖明, 杜寿文. 从禽类黏膜免疫系统洞悉禽流感黏膜疫苗研发策略[J]. 生物技术通报, 2026, 42(7): 48-57.

ZHU Mei-wei, ZHANG Jian-feng, WANG Jia-min, LIAO Ming, DU Shou-wen. Strategies for Avian Influenza Mucosal Vaccine Development： Insights from the Avian Mucosal Immune System[J]. Biotechnology Bulletin, 2026, 42(7): 48-57.

图/表 2

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宿主 Host	疫苗 Vaccine	接种方式 Vaccination method	组份 Composition	靶病原 Target pathogen	参考文献 References
鸡	禽流感、新城疫二联活疫苗（rLH5-8株）	滴鼻/点眼/饮水/肌肉注射	鸡NDV（La Sota株）、禽流感H5亚型	NDV、AIV	［44］
鸡	重组HVT活疫苗（rHVT-H9-F）	肌肉/皮下注射/胚内接种	H9N2（A/chicken/Israel/1164/2011）、HVT、NDV F蛋白	AIV、NDV	［49］
鸡	禽流感重组FPV载体活疫苗（H5亚型）	皮下注射/肌肉注射/翅蹼穿刺	AIV鹅体分离株（G5株）、FPV（282E4株）	AIV、FPV	［51］
鸭	禽流感重组DVE载体二价活疫苗（H5亚型，rDEV-13株+rDEV-14株）	肌肉注射	禽流感重组DEV rDEV-13株和rDEV-14株	AIV、DEV	［53］

宿主 Host	疫苗 Vaccine	接种方式 Vaccination method	组份 Composition	靶病原 Target pathogen	参考文献 References
鸡	禽流感、新城疫二联活疫苗（rLH5-8株）	滴鼻/点眼/饮水/肌肉注射	鸡NDV（La Sota株）、禽流感H5亚型	NDV、AIV	［44］
鸡	重组HVT活疫苗（rHVT-H9-F）	肌肉/皮下注射/胚内接种	H9N2（A/chicken/Israel/1164/2011）、HVT、NDV F蛋白	AIV、NDV	［49］
鸡	禽流感重组FPV载体活疫苗（H5亚型）	皮下注射/肌肉注射/翅蹼穿刺	AIV鹅体分离株（G5株）、FPV（282E4株）	AIV、FPV	［51］
鸭	禽流感重组DVE载体二价活疫苗（H5亚型，rDEV-13株+rDEV-14株）	肌肉注射	禽流感重组DEV rDEV-13株和rDEV-14株	AIV、DEV	［53］