Viral Burden: New insights into Estimating IgG Recognition Across Human Populations

Assessment of viral burden in populations is essential for understanding virus epidemiology and herd immunity potential. While serological profiling is straightforward at the individual level, it remains challenging at scale. We propose analysis advancing in serological technologies for broader population-level analysis and comparison. We used an epitope library in Phage Display ImmunoPrecipitation (PhIP) technology (VirScan type library) to assess IgG recognition of 49,630 representative viral oligopeptides in 134 serum samples from two populations (Poland and the US). Only 5.9% of oligopeptides were immunogenic, yet IgG recognition of viruses was consistent across populations - over 90% of virus species, 99% of genera, and 97% of families were detected. Shannon Diversity Index analysis supported these findings. Among immunogenic peptides, 9.1% were significantly more frequently recognized, though not correlated with recognition strength. We further proposed a normalization method to account for differences in viral proteome representation when assessing immune burden: the burden score. Finally, we demonstrated how this approach facilitates serological comparisons between populations. These observations show that while people are exposed to similar viruses, they produce antibodies against different viral epitopes. This individual variability, combined with broad virus recognition, likely strengthens population-level protection. Epitope recognition frequency seems to be shaped more by population exposure than by magnitude of response that an epitope can induce. Accurately measuring viral burden can inform healthcare planning, and antiviral technologies development.