Comprehensive serological profiling of human populations using a synthetic human virome (VirScan)

Most antibody assays in clinical and research use are designed to ask one question at a time: is there an antibody response to this specific pathogen, yes or no? The authors of this paper built a different kind of assay. They synthesized 93,904 DNA oligonucleotides on a programmable microarray, encoding 56-amino-acid peptide tiles with 28-residue overlaps that together span the reference proteomes of every virus in UniProt annotated as having human tropism — 206 species and over 1,000 strains. They cloned this library into a T7 bacteriophage display vector, incubated it with serum, used protein A/G beads to recover antibody-bound phage, and read the surviving phage by PCR and massively parallel DNA sequencing.

The assay, named VirScan, requires only about 1 µL of serum (2 µg of immunoglobulin) per sample, runs in 96-well format on a liquid handler, and produces a virome-wide antibody profile for roughly $25 per sample. Applied to 569 donors from the United States, Peru, Thailand, and South Africa, VirScan produced more than 100 million antibody–peptide interaction measurements — the first comprehensive, epitope-resolved view of the antiviral antibody repertoire across an entire human virome.

The findings reframed how to think about adult antiviral immunity. The average adult carried antibody responses against the proteins of about ten different virus species, with some individuals showing detectable antibodies against more than 25. Antibody profiles correlated with HIV status and geographic origin, and many of the most prominent epitopes were shared (“public”) across diverse populations — converging on the same residues despite the donors’ different exposure histories and genetic backgrounds. VirScan established the foundational platform for the entire family of programmable phage-display antibody-reactome assays that Infinity Bio and others have since extended to allergens, autoantigens, bacteria, and the complete human virome.