Reconstructing pathogen-specific antibody binding epitopes and age-dependent immune signatures from proteomic-scale peptide libraries
High-density peptide arrays are useful for mapping linear antibody epitopes and resolution of antibody specificity in a single-assay platform. Here, we used peptide library screening to evaluate magnitude and breadth of humoral responses to enteric pathogens in the context of public health interventions. We characterized the epitope landscape to known immunogenic proteins to several viruses, bacteria, and parasites and used that to infer immunological profiles at age 3, 14, and 28 months. The peptide libraries detected immune signatures better for viruses compared with bacteria and parasites and captured distinct dynamics of protein-level variation in immune signatures over time. We found limited sensitivity for bacterial and protozoan pathogens whose humoral responses may depend more on conformational or natively modified epitopes than linear-peptide binding. Unbiased peptide libraries have potential utility for broad analysis of antibody responses in integrated serosurveillance, but our results reveal pathogen-specific limitations where peptide-based serology would be less predictive of true infection status and where it would provide greater surveillance value. Beyond assay performance, peptide arrays are useful for studying epitope architecture, and a practical implication would require augmentation with alternative antigen formats (whole-protein or folded antigens) in a complementary hybrid approach.
Authors
- Benjamin F. Arnold (ORCID: https://orcid.org/0000-0001-6105-7295)
- Andrew N. Mertens (ORCID: https://orcid.org/0000-0002-1050-6721)
- Jack Reifert (ORCID: https://orcid.org/0000-0001-5421-7756)
- Richelle C. Charles (ORCID: https://orcid.org/0000-0002-8881-1849)
- Daniel T. Leung (ORCID: https://orcid.org/0000-0001-8401-0801)
- Jessica A. Grembi (ORCID: https://orcid.org/0000-0001-6142-4913)
- Nikolina Walas (ORCID: https://orcid.org/0000-0002-6137-9275)
- Md Ziaur Rahman (ORCID: https://orcid.org/0000-0002-8058-4602)
- Minlu Zhang (ORCID: https://orcid.org/0000-0003-2347-0569)
- Stephen P. Luby (ORCID: https://orcid.org/0000-0001-5385-899X)
- Syeda L Famida
- John Shon (ORCID: https://orcid.org/0000-0001-9465-6286)
- Audrie Lin (ORCID: https://orcid.org/0000-0002-3877-3469)
- Abul K. Shoab (ORCID: https://orcid.org/0000-0002-6497-1661)
- Shahjahan Ali (ORCID: https://orcid.org/0000-0003-3883-1208)
- Kathy Kamath (ORCID: https://orcid.org/0000-0001-6143-3414)
- Palash Mutsuddi
- Everlyn Kamau (ORCID: https://orcid.org/0000-0003-4285-2255)
- Mahbubur Rahman (ORCID: https://orcid.org/0000-0001-8577-8281)
- Salma Akther
- Md Saheen Hossen
Institutions
- Uppsala University (SE)
- Pennsylvania State University (US)
- Harvard University (US)
- Colorado School of Public Health (US)
- University of California, San Francisco (US)
- University of California, Santa Cruz (US)
- International Centre for Diarrhoeal Disease Research (BD)
- University of Utah (US)
- San Francisco Foundation (US)
- Massachusetts General Hospital (US)
- Serimmune (United States) (US)
- Berkeley Public Health Division (US)
- Global Brain Health Institute (US)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-08-19
- DOI
- https://doi.org/10.1126/sciadv.aec5478
- Citations
- 1
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 3.26
Funders
- National Institutes of Health