Nuclear Genome Amplification of Antibody VDJ Regions in Wastewater

Wastewater-based epidemiology (WBE) has become a valuable tool to monitor pathogens from community and municipal sources. Whereas the detection of a pathogen in wastewater can help public health agencies understand what is present in a community, it cannot provide insight into a populations preexisting immunity. Genomic rearrangement of the VDJ region of the human genome generates antibody diversity, a critical step in human immunity. We hypothesized that human antibody genes could be amplified from wastewater and sequenced, providing a snapshot of a populations antibody repertoire. Here, we report the successful amplification and sequencing of human immunoglobulin heavy and light chain variable regions from wastewater. We observed a diverse range of sequence polymorphisms in these reads, suggesting the presence of distinct antibody sequences from various clonal lineages. The sequences aligned to conserved structural regions as well as the more variable complementarity-determining regions (CDRs). Additionally, we aligned the wastewater reads to two databases of antibodies with known functions. The wastewater reads encoded the conserved CDRs1 and 2, but diverged at the CDR3 sites, which determine epitope binding. Collectively, these findings serve as proof of principle that wastewater analysis may extend beyond pathogen detection to the characterization of population immunity and human genetics more broadly.