流感减毒活疫苗的研究进展 ——从经验减毒到理性设计

Research Progress on Live Attenuated Influenza Vaccines: From Empirical Attenuation to Rational Design

摘要

流感病毒感染已严重威胁人类健康，接种疫苗仍是目前防控流感最有效的措施之一。流感减毒活疫苗（live attenuated influenza vaccine，LAIV）通过鼻腔接种模拟自然感染，可同时诱导体液、细胞和呼吸道黏膜免疫，是开发广谱流感疫苗的重要技术平台之一。近年来，随着反向遗传学、合成生物学和基因工程技术的发展，LAIV 研发逐渐由传统经验性减毒向基于病毒致病机制及宿主-病毒互作的理性设计转变。综述近年来甲型流感 LAIV 的主要理性设计策略，分析其减毒机制、病毒复制、安全性及免疫保护特点，并讨论其临床转化面临的挑战与发展前景，为后续减毒策略的优化、新型 LAIV 的研发及其临床转化提供参考。总体而言，理性设计为构建更安全、高效、广谱及快速响应的 LAIV 提供了新的技术路径，有望成为推动流感疫苗创新研发的重要方向。

Abstract

Influenza virus infection poses a serious threat to human health, and vaccination remains one of the most effective measures for influenza prevention and control. Live attenuated influenza vaccine (LAIV), administered intranasally to mimic natural infection, can simultaneously induce humoral, cellular, and respiratory mucosal immunity, and represents an important technological platform for the development of broad-spectrum influenza vaccines. In recent years, with advances in reverse genetics, synthetic biology, and genetic engineering, LAIV development has gradually shifted from traditional empirical attenuation toward rational design based on viral pathogenic mechanisms and host-virus interactions. This review systematically summarizes the major rational design strategies for influenza A LAIVs in recent years, analyzes their attenuation mechanisms, viral replication characteristics, safety and immune-protection profiles, and discusses the challenges and prospects of their clinical translation, to provide a reference for optimizing future attenuation strategies and for the development and clinical translation of novel LAIVs. Overall, rational design provides a new technological pathway for developing safer, more effective, broad-spectrum, and rapid-response LAIVs and is expected to be an important direction for advancing innovative research and development of influenza vaccines.

关键词

流感减毒活疫苗 / 理性设计 / 减毒机制 / 甲型流感病毒

Key words

live attenuated influenza vaccines / rational design / attenuation mechanisms / influenza A virus

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基金资助

深圳市医学研究专项资金项目(B2303001)