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

The founding VirScan paper: a programmable phage-display library that maps antibody responses to every known human-tropic virus from 1 µL of serum.

Xu GJ, Kula T, Xu Q, Li MZ, Vernon SD, Ndung’u T, Ruxrungtham K, Sanchez J, Brander C, Chung RT, O’Connor KC, Walker B, Larman HB, Elledge SJ.

Science · June 5, 2015 · DOI: 10.1126/science.aaa0698

How to cite

AMA

Xu GJ, Kula T, Xu Q, et al. Comprehensive serological profiling of human populations using a synthetic human virome. Science. 2015;348(6239):aaa0698. doi:10.1126/science.aaa0698

APA

Xu, G. J., Kula, T., Xu, Q., Li, M. Z., Vernon, S. D., Ndung’u, T., Ruxrungtham, K., Sanchez, J., Brander, C., Chung, R. T., O’Connor, K. C., Walker, B., Larman, H. B., & Elledge, S. J. (2015). Comprehensive serological profiling of human populations using a synthetic human virome. Science, 348(6239), aaa0698. https://doi.org/10.1126/science.aaa0698

BibTeX

@article{xu2015virscan,
  title   = {Comprehensive serological profiling of human populations using a synthetic human virome},
  author  = {Xu, George J. and Kula, Tomasz and Xu, Qikai and Li, Mamie Z. and Vernon, Suzanne D. and Ndung'u, Thumbi and Ruxrungtham, Kiat and Sanchez, Jorge and Brander, Christian and Chung, Raymond T. and O'Connor, Kevin C. and Walker, Bruce and Larman, H. Benjamin and Elledge, Stephen J.},
  journal = {Science},
  volume  = {348},
  number  = {6239},
  pages   = {aaa0698},
  year    = {2015},
  doi     = {10.1126/science.aaa0698}
}

The original VirScan paper. Xu, Kula, Larman, Elledge and colleagues introduced a programmable phage-display library encoding 56-residue peptide tiles spanning the proteomes of all 206 known human-tropic virus species, then assayed more than 100 million antibody–peptide interactions in 569 donors across four continents to produce the first virome-wide, epitope-resolved map of antiviral antibody responses ever published.

Read publication at Science

In this publication:

VirScan T7 phage library encodes 93,904 200-mer DNA oligonucleotides as 56-aa peptide tiles with 28-residue overlaps spanning all 206 human-tropic virus species and over 1,000 strains.
Adults carried antibody responses to a median of ten virus species; some donors had detectable antibodies against more than 25 distinct viruses.
Public epitopes were broadly conserved — 569 donors across four continents (United States, Peru, Thailand, South Africa) showed strikingly convergent epitope recognition for many common viruses.
Each VirScan run requires only ~1 µL of serum (2 µg IgG), runs in 96-well format on a liquid handler, and costs roughly $25 per sample.

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.

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

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