Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi, India.
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, Dhaula Kuan, New Delhi, India.
Adv Protein Chem Struct Biol. 2024;140:59-90. doi: 10.1016/bs.apcsb.2023.12.020. Epub 2024 Mar 7.
It is critical to emphasize the importance of vaccination as it protects us against harmful pathogens. Despite significant progress in vaccine development, there is an ongoing need to develop vaccines that are not only safe but also highly effective in protecting against severe infections. Subunit vaccines are generally safe, but they frequently fail to elicit strong immune responses. As a result, there is a need to improve vaccine effectiveness by combining them with adjuvants, which have the potential to boost the immune system many folds. The process of developing these adjuvants requires searching for molecules capable of activating the immune system, combining these promising compounds with an antigen, and then testing this combination using animal models before approving it for clinical use. Liposomal adjuvants work as delivery adjuvants and its activity depends on certain parameters such as surface charge, vesicle size, surface modification and route of administration. Self-assembly property of peptide adjuvants and discovery of hybrid peptides have widened the scope of peptides in vaccine formulations. Since most pathogenic molecules are not peptide based, phage display technique allows for screening peptide mimics for such pathogens that have potential as adjuvants. This chapter discusses about peptide and liposome-based adjuvants focusing on their properties imparting adjuvanticity along with the methods of formulating them. Methods of adjuvant characterization important for an adjuvant to be approved for clinical trials are also discussed. These include assays for cytotoxicity, T-lymphocyte proliferation, dendritic cell maturation, cytokine and antibody production, toll-like receptor dependent signaling and adjuvant half-life.
必须强调接种疫苗的重要性，因为它可以保护我们免受有害病原体的侵害。尽管疫苗开发取得了重大进展，但仍需要开发不仅安全而且在预防严重感染方面非常有效的疫苗。亚单位疫苗通常是安全的，但它们常常不能引起强烈的免疫反应。因此，需要通过与佐剂结合来提高疫苗的有效性，佐剂有潜力使免疫系统增强多倍。开发这些佐剂的过程需要寻找能够激活免疫系统的分子，将这些有前途的化合物与抗原结合，然后在批准用于临床使用之前使用动物模型进行测试。脂质体佐剂作为递送佐剂起作用，其活性取决于某些参数，如表面电荷、囊泡大小、表面修饰和给药途径。肽佐剂的自组装特性和杂合肽的发现拓宽了肽在疫苗配方中的应用范围。由于大多数致病分子不是基于肽的，噬菌体展示技术允许筛选针对此类病原体的肽模拟物，这些模拟物具有作为佐剂的潜力。本章讨论了基于肽和脂质体的佐剂，重点介绍了它们赋予佐剂特性的特性，以及它们的配方方法。还讨论了佐剂特征的方法，这些方法对于佐剂获得临床试验批准很重要。这些方法包括细胞毒性、T 淋巴细胞增殖、树突状细胞成熟、细胞因子和抗体产生、 toll 样受体依赖性信号传导和佐剂半衰期的测定。
