Virus-like particle vaccines: from antigen architecture to antigen presentation and adaptive immune responses

Virus-like particles (VLPs) mimic key structural features of native viruses while lacking a replication-competent viral genome, combining favorable safety with multivalent antigen presentation and strong immunogenicity. Yet, how VLP design influences the quality and persistence of adaptive immunity remains incompletely understood.

This review examines relevant literature identified through targeted searches on recent advances in VLP engineering, with emphasis on particle architecture, antigen-display strategies, and structural determinants of immune recognition. We discuss how VLPs facilitate antigen presentation by antigen-presenting cells and shape CD4⁺ and CD8⁺ T-cell responses, immune memory, and T follicular helper cell-B-cell interactions within germinal centers. Emerging approaches linking VLP design with humoral and cellular immunity are also considered.

The next generation of VLP vaccines will require a transition from empirical enhancement of immunogenicity toward precision engineering of immune responses. A major challenge is to establish robust and transferable structure-immunity relationships while addressing manufacturing feasibility, quality control, potency assessment, and product comparability. Advances in computational protein design, structural biology, and high-dimensional immune profiling are expected to enable increasingly quantitative and mechanism-based optimization of VLP platforms. However, fully predictive control over human immune responses will remain a complex challenge.