Progress in Protein Nanoparticle Vaccines for Human Viral Diseases

In the development of antiviral vaccines, insufficient immunogenicity and limited cross-protective efficacy against rapidly evolving viruses remain as major challenges. Protein nanoparticle vaccine platforms have emerged as a promising strategy because of their capacity for multivalent antigen presentation, structural stability, and enhanced immunogenicity. Both naturally occurring and computationally designed protein nanoparticles, including ferritin, lumazine synthase, E2p, I53-50, I301, and mi3, have been widely investigated for the presentation of diverse viral antigens. In this review, we summarize recent advances in protein nanoparticle vaccines for major human viral diseases, with emphasis on how nanoparticle geometry, assembly architecture, and antigen-display strategies influence immunogenicity and broad-spectrum immune responses. We further discuss recent progress in mosaic antigen display, germline-targeting immunogens, and clinically translated nanoparticle vaccine platforms together with current challenges and future directions in scaffold engineering and vaccine design. Protein nanoparticle platforms provide a versatile foundation for structure-guided antiviral-vaccine development.