Department of Biology, The Catholic University of America, Washington, DC 20064, USA; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Adv Drug Deliv Rev. 2019 May;145:57-72. doi: 10.1016/j.addr.2018.06.025. Epub 2018 Jul 6.
Subunit vaccines containing one or more target antigens from pathogenic organisms represent safer alternatives to whole pathogen vaccines. However, the antigens by themselves are not sufficiently immunogenic and require additives known as adjuvants to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes in a more native context. The repetitive, symmetrical, and high density display of antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria and viruses. The antigens, thus, might be better presented to stimulate host's innate as well as adaptive immune systems thereby eliciting both humoral and cellular immune responses. Bacteriophages such as phage T4 provide excellent platforms to generate the nanoparticle vaccines. The T4 capsid containing two non-essential outer proteins Soc and Hoc allow high density array of antigen epitopes in the form of peptides, domains, full-length proteins, or even multi-subunit complexes. Co-delivery of DNAs, targeting molecules, and/or molecular adjuvants provides additional advantages. Recent studies demonstrate that the phage T4 VLPs are highly immunogenic, do not need an adjuvant, and provide complete protection against bacterial and viral pathogens. Thus, phage T4 could potentially be developed as a "universal" VLP platform to design future multivalent vaccines against complex and emerging pathogens.
亚单位疫苗包含一种或多种来自病原体的目标抗原，代表了比全病原体疫苗更安全的选择。然而，这些抗原本身的免疫原性并不足够，需要添加所谓的佐剂来增强免疫原性和保护效果。将抗原组装成病毒样纳米颗粒 (VLPs) 是一种更好的方法，因为它允许以更天然的形式展示表位。VLPs 上抗原的重复、对称和高密度展示模拟了细菌和病毒上存在的病原体相关分子模式。因此，抗原可能会更好地呈现出来，刺激宿主的先天和适应性免疫系统，从而引发体液和细胞免疫反应。噬菌体如 T4 噬菌体为生成纳米颗粒疫苗提供了极好的平台。T4 衣壳含有两个非必需的外壳蛋白 Soc 和 Hoc，允许以肽、结构域、全长蛋白甚至多亚基复合物的形式高密度排列抗原表位。共递送 DNA、靶向分子和/或分子佐剂提供了额外的优势。最近的研究表明，噬菌体 T4 VLP 具有高度的免疫原性，不需要佐剂，并且可以完全预防细菌和病毒病原体。因此，噬菌体 T4 有可能被开发为“通用”VLP 平台，用于设计针对复杂和新兴病原体的未来多价疫苗。
