Self-Assembling protein nanoparticle platform for multivalent antigen delivery in vaccine development

Nanoparticle vaccines can efficiently and repeatedly display multivalent antigens, thereby improving the targeted delivery of antigens and inducing more durable immune responses, making them an important representative of novel vaccines. The global COVID-19 pandemic has accelerated the development of nanoparticle vaccines, offering a promising solution for the prevention and control of infectious diseases. Currently, the development of nanoparticle vaccines involves the use of various types of nanoparticles, including liposomes, polymers, inorganic materials, and emulsions. Protein nanoparticles candidate vaccines are attracting increasing attention because of their unique antigen presentation methods and self-assembly characteristics during their development, leading to a broad consensus on their promising future. Naturally self-assembling protein nanoparticles, such as ferritin, enhance antigen presentation, which aids in the activation of both humoral and cellular immune responses. This has led to significant advancements in the study of hepatitis B virus. Meanwhile, some synthetically engineered protein nanoparticles, such as mi3, and I53-50, can induce higher antibody titers through chemical conjugation with the SpyTag-SpyCatcher system, thereby providing better immunoprotection and showing promising prospects in the prevention of H1N1 and H3N2 influenza virus infections. This article reviews the unique advantages of protein nanoparticles as antigen delivery platforms, progress made in immunological design mechanisms, advances in the application of related adjuvants in preclinical and clinical trials, and the performance of commonly used computationally designed protein nanoparticles in preclinical trials, with a particular emphasis on the progress in the application of cationic nanoparticle vaccines. The aim is to provide future researchers with effective adjuvant strategies and high-quality selections for computationally designed protein nanoparticles, thereby promoting the clinical trial process of protein nanoparticles vaccines.