Abstract
One hundred and sixty-five years ago, Charles Darwin's observations of homologous structures in finch beaks laid the groundwork for evolutionary biology. Today, his evolutionary theory has been extended to the microscopic scale, where homologous structures in viral capsids reveal pathogen-associated geometric pattern (PAGP). PAGP is the highly conserved geometric signature characteristic of an entire class of microbes like viruses or bacteria. These repetitive and highly organized structures reflect evolutionary convergence shaped by natural selection. PAGPs, including the size and geometric arrangement of multivalent antigen displays, enhance host immune system’s ability to recognize recurring structural features in pathogens. Both innate and adaptive immunity can recognize and respond to PAGPs through high-avidity multivalent interactions, leading to the robustness of PAGP-induced immune responses. Beyond advancing our understanding of pathogen evolution and host immune defenses, PAGPs also inspire bioengineered innovations in modern vaccinology, offering new strategies to mimic natural PAGPs to strike a balance between efficacy and safety in immune activation.
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