SIMPLE SUMMARY: Determining the exposure or infection history of a person to a multitude of viruses is not an easy task. Typically, antibody tests detect antibodies against proteins (antigens) to only one or a few viruses. Here, we review an emerging technology called Phage ImmunoPrecipitation Sequencing (PhIP-Seq), that allows us to study the infection history of individuals to large numbers of viruses simultaneously. This technology uses bacteriophages to express and display viral antigens of choice, which are then bound by antigen-specific antibodies in patient samples. Antibody-bound bacteriophages are pulled down and identified through molecular techniques. This technology has been used in various infectious disease scenarios, including assessing exposure to different viruses, studying vaccine responses, and identifying viral cause of diseases. Despite inherent limitations in presenting only peptides, this technology holds great promise for future application in identifying novel pathogens, one health and pandemic preparedness. ABSTRACT: Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a high throughput serological technology that is revolutionizing the manner in which we track antibody profiles. In this review, we mainly focus on its application to viral infectious diseases. Through the pull-down of patient antibodies using peptide-tile-expressing T7 bacteriophages and detection using next-generation sequencing (NGS), PhIP-Seq allows the determination of antibody repertoires against peptide targets from hundreds of proteins and pathogens. It differs from conventional serological techniques in that PhIP-Seq does not require protein expression and purification. It also allows for the testing of many samples against the whole virome. PhIP-Seq has been successfully applied in many infectious disease investigations concerning seroprevalence, risk factors, time trends, etiology of disease, vaccinology, and emerging pathogens. Despite the inherent limitations of this technology, we foresee the future expansion of PhIP-Seq in both investigative studies and tracking of current, emerging, and novel viruses. Following the review of PhIP-Seq technology, its limitations, and applications, we recommend that PhIP-Seq be integrated into national surveillance programs and be used in conjunction with molecular techniques to support both One Health and pandemic preparedness efforts.
Phage ImmunoPrecipitation Sequencing (PhIP-Seq): The Promise of High Throughput Serology