Advancing viral detection: Recent progress in phage immunoprecipitation sequencing (PhIP-Seq) for immune profiling and surveillance

Global efforts to characterize emerging or reemerging viruses from wildlife strongly depend on comprehensive detection platforms based on highly multiplexed serology. With the rising risk of new pandemics, there is an increasing need for improved strategies to track infection progression, assess exposure history, and evaluate vaccine-induced immune responses. In this review, we examine advancements in Phage Immunoprecipitation Sequencing (PhIP-Seq) for viral surveillance and immune profiling. PhIP-Seq enables the detailed analysis of hundreds of viral proteomes at the epitope level, processing multiple samples simultaneously with minimal sample input relative to the extensive pool of antigen targets in serological surveys. Recent advancements in this technique have significantly enhanced our ability to detect emerging viral pathogens, providing new insights into viral immunity and epidemiology. While PhIP-Seq still relies on serological testing and thus shares some limitations, such as dependency on antibody kinetics and potential cross-reactivity, its high multiplexing capacity and data-driven insights makes it a useful tool for large-scale epidemiological surveillance and immune response characterization. Short Schematic workflow of Phage Immunoprecipitation Sequencing (PhIP-Seq)