Abstract
Pathogen evolution and narrow vaccine coverage urgently demand broad-spectrum vaccines. This review explores two pivotal technological fronts: structural biology- and immunoinformatics-guided antigen design, and utilizing nanoparticle-based delivery systems to induce broad immune responses. We critically analyze four antigen optimization strategies: (i) structure-based antigen design, (ii) conserved epitope targeting, (iii) consensus sequence-based antigen engineering, and (iv) chimeric immunogen design. Additionally, the common types and characteristics of nanoparticles are described briefly. Subsequently, we delve into cutting-edge applications of nanoparticles to enhance immune protection, including mosaic and cocktail nanoparticle vaccines, surface-modified targeting strategies, and the integration of mRNA technology with virus-like particles (VLPs). In conclusion, this review synthesizes risk-benefit analyses of existing strategies, current challenges, and emerging opportunities, offering practical frameworks to facilitate broad-spectrum vaccine innovation and enhance pandemic preparedness.