Multiepitope Fusion Antigen: MEFA, an Epitope- and Structure-Based Vaccinology Platform for Multivalent Vaccine Development.
Multiepitope Fusion Antigen: MEFA, an Epitope- and Structure-Based Vaccinology Platform for Multivalent Vaccine Development.
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DOI：
10.1007/978-1-0716-1900-1_10
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发表时间：
2022
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疫苗被认为是对抗传染病最具成本效益的对策。经常影响疫苗开发的一个挑战是抗原多样性或病原体异质性。不同的菌株产生免疫上异质性的毒力因子，因此有效的疫苗需要诱导广谱宿主免疫来提供交叉保护。基因组学和蛋白质组学，特别是计算生物学和结构生物学的最新进展，建立了结构疫苗学，并强调了开发有效和精确疫苗的可行性。本文介绍了基于表位和结构的多表位融合抗原（multiepitope-fusion-antigen， MEFA）疫苗学平台，并提供了用于疫苗开发的多价MEFA免疫原的制备指导。从概念上讲，MEFA结合了表位疫苗学和结构疫苗学，使蛋白质免疫原能够呈现异质抗原结构域（表位），并诱导针对不同毒力因子、菌株或疾病的广泛保护性免疫。在方法上，MEFA平台首先从异种菌株或感兴趣的毒力因子中鉴定出安全、结构稳定且具有强免疫原性的骨干蛋白和免疫优势（理想中和或保护性）表位。然后，在蛋白质建模和分子动力学模拟的辅助下，MEFA通过取代多价MEFA蛋白的表位，将异质表位整合到一个骨干蛋白中，并模拟表位的天然抗原性。最后，MEFA蛋白在动物免疫中进行了广泛的免疫原性检测，并评估了临床前研究中多价疫苗开发的潜在应用。
Vaccines are regarded as the most cost-effective countermeasure against infectious diseases. One challenge often affecting vaccine development is antigenic diversity or pathogen heterogeneity. Different strains produce immunologically heterogenous virulence factors, therefore an effective vaccine needs to induce broad-spectrum host immunity to provide cross protection. Recent advances in genomics and proteomics, particularly computational biology and structural biology, establishes structural vaccinology and highlights the feasibility of developing effective and precision vaccines. Here, we introduce the epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA), and provide instructions to generate multivalent MEFA immunogens for vaccine development. Conceptually, MEFA combines epitope vaccinology and structural vaccinology to enable a protein immunogen to present heterogenous antigenic domains (epitopes) and to induce broadly protective immunity against different virulence factors, strains or diseases. Methodologically, the MEFA platform first identifies a safe, structurally stable and strongly immunogenic backbone protein and immunodominant (ideally neutralizing or protective) epitopes from heterogenous strains or virulence factors of interest. Then, assisted with protein modeling and molecule dynamic simulation, MEFA integrates heterogeneous epitopes into a backbone protein via epitope substitution for a multivalent MEFA protein and mimics epitope native antigenicity. Finally, the MEFA protein is examined for broad immunogenicity in animal immunization, and assessed for potential application for multivalent vaccine development in preclinical studies.