疫苗的结构基础和分子设计  

Structural basis and molecular design of vaccines

作　　者：李婷婷 顾颖[1] 李少伟[1] LI Tingting;GU Ying;LI Shaowei(National Institute of Diagnostics and Vaccine Development in Infectious Diseases,School of Public Health,School of Life Sciences,Xiamen University,Xiamen 361102,China)

机构地区：[1]厦门大学公共卫生学院,生命科学学院,国家传染病诊断试剂与疫苗工程技术研究中心,福建厦门361102

出　　处：《厦门大学学报（自然科学版）》2024年第3期369-377,共9页Journal of Xiamen University：Natural Science

基　　金：国家重点研发计划(2021YFC2301404)。

摘　　要：[背景]结构疫苗学方法是逆向疫苗学的逻辑演进,其核心是利用保护性决定因子来有选择地设计抗原,进而重新设计和简化,以纳入疫苗组合中.该技术旨在开发创新性传染病疫苗和设计具有广谱保护的疫苗免疫原,尤其对于目前仍无疫苗能用于防控的艾滋病毒(HIV)、寨卡病毒、结核杆菌及多种耐药菌引发的严重威胁人类健康的传染病具有重大应用前景.[进展]目前重大传染病疫苗的研发困难主要集中在病原体抗原表位的变异性,然而随着利用结构生物学疫苗设计的初步成功,结构疫苗学技术在疫苗研发陷入困境的情况下展现出巨大的应用潜力.许多重要病原体如HIV、新型冠状病毒、流感病毒的抗体-抗原复合物结构得到解析,许多有潜力的候选抗原表位陆续被发现.本文主要介绍疫苗的结构基础和如何基于结构进行理性分子设计.[展望]如何将这些表位应用于抗原改造,设计出保护性集中的免疫原或疫苗是结构疫苗学下一步需要努力的目标.结构疫苗学结合现代计算和人工智能技术的应用,可为21世纪的医学和科技挑战提供前所未有的解决方案,疫苗研发领域有望实现重大飞跃.[Background]Structural vaccinology represents the natural progression from reverse vaccinology,leveraging genome-based methodologies and structural biology techniques to selectively design antigens using protective determinants.These antigens are further refined and simplified for vaccine formulation integration.The primary aim of this approach is to engineer innovative vaccines that offer broad-spectrum protection against infectious diseases,addressing the current lack of vaccines for pathogens such as human immunodeficiency virus(HIV),Zika virus,tuberculosis,and multiple antibiotic-resistant bacteria,all of which pose severe threats to public health.Moreover,structural vaccinology harnesses a genomic approach that merges information from diverse disciplines,including immunology,biochemistry,molecular biology,and structural biology,to guide vaccine development through the analysis of three-dimensional structures of pathogens surface proteins or components.Leveraging advanced structural biology techniques such as X-ray crystallography,nuclear magnetic resonance(NMR)spectroscopy,and cryo-electron microscopy(Cryo-EM),scientists can elucidate the intricate molecular structures of pathogen antigens.This understanding facilitates a deeper insight into the interaction mechanisms between pathogens and the host immune system.[Progress]The variability of antigenic epitopes in pathogens constitutes a significant hurdle in vaccine development for infectious diseases.However,the early successes in applying structural biology to vaccine design underscore the immense potential of structural vaccinology,particularly in challenging scenarios of vaccine development.The elucidation of antibody-antigen complex structures for critical pathogens,including HIV,COVID-19,and influenza,has yielded a wealth of potentially viable epitopes.Several representative examples underscore the structure-based vaccine molecular designs.The discovery of the respiratory syncytial virus(RSV)F protein s pre-fusion(pre-F)conformation has emerged as a pri

关 键 词：结构疫苗学 保护性表位 免疫原 免疫复合物 疫苗设计 

分 类 号：Q31[生物学—遗传学]