The Viral Burden: population-wide IgG recognition of viral proteomes and geographic variation

Introduction: The immune system indexes prior viral exposures through the development of immunological memory, providing long-term protection against subsequent infections. Objectives: We use the VirScan technology to probe the diversity of the human immune response to viral infections by analyzing serological profiles. Methods: We evaluated IgG recognition from 135 serum samples collected in Poland and the United States, to 49,630 oligopeptide sequences representing known viral proteomes. Results: In our dataset, only 5.9% of these oligopeptides were recognized as immunogenic by IgG antibodies. Nonetheless, recognition patterns were highly specific and non-random, with an average of 90 ± 21 immunogenic oligopeptides identified per serum sample. Despite individual variability, the recognition of viral species, genera, and families remained consistent across populations, with over 90% of tested viral species, 99% of genera, and 97% of families recognized by our serum samples. The Shannon Diversity Index indicated a low diversity at the viral oligopeptides (epitopes) level, but a normal, random diversity at the species, genera, and family levels. Geographical comparisons revealed several differences in serological profiles between Polish and American samples, yet the overall recognition of viral species was similar between the two populations. Conclusion: Our findings suggest a diverse array of viral epitopes, rather than few strong epitopes, may enhance immune responses across populations, which has implications for vaccine development and for epidemiological predictions. We also identify a small subset of viruses that exerted the most burden on the immune system, providing epidemiological insight for healthcare planning. Our analysis underscores the complexity of the human immune response, suggesting that a wide range of viral epitopes can bolster population-level immunity against viruses.