Biology subjects

Harhala, M.

Publications and source records attributed to Harhala, M..

3 recordsLinked to original sources

bioRxiv2026

A synthetic phageome reveals widespread and diverse human antibody responses to bacteriophages

Bacteriophages colonize humans, yet their recognition by humoral immunity remains unclear. We developed PhageScan, a PhIP- Seq platform comprising 277,051 phage and 49,630 human viral oligopeptides. Profiling sera from 192 healthy donors without prior phage therapy characterized anti-phage response specificity and revealed widespread, strong IgG reactivity to phages, comparable in prevalence and magnitude to that against human viruses. Recognition patterns were however highly individualized. Among phage sequences, 12,576 peptides were significantly enriched in at least two individuals. Strongly immunogenic epitopes preferentially originated from phages infecting pathogenic bacteria, whereas widely shared ''public'' epitopes were enriched among phages of environmental and food-associated bacteria. ImmE, a lactococcal phage endolysin recognized in 59.9% of individuals, showed reduced antibacterial activity in the presence of sera identified as ImmE-reactive by PhageScan, demonstrating functional relevance. These findings establish phage-directed antibodies as a widespread component of human immunity and PhageScan as a scalable platform for defining phage--antibody interactions.

immunology↗

bioRxiv2024

Phageome transfer from gut to circulation and its regulation by human immunity

Bacteriophages dominate the human gut virome, yet their presence in the bloodstream remains orders of magnitude lower, suggesting that systemic dissemination is tightly regulated. How gut phages cross the intestinal barrier and which factors govern their persistence in circulation remain poorly understood, largely because prior studies characterized gut and blood viromes independently rather than in matched samples from the same individuals. Here we investigated phage translocation by shotgun metagenomics of matched colon mucosal biopsies and sera from 37 individuals with phage specific IgG profiling using a pan-phage proteome-derived phage display epitope library, complemented by an oral T4 model in mice. We found that phage abundance decreased by approximately 98% from intestinal mucosa to serum. The mucosal virome was dominated by Microviridae, which also accounted for most of the translocated phages. In the mouse model, phage titers dropped stepwise by [~]106 fold from gut content to blood, with the sharpest reduction occurring at the mucosal-lymphatic interface. Among translocated viral operational taxonomic units 93.1% lacked taxonomic assignment, yet network analysis revealed reproducible co-enrichement with annotated families including Herelleviridae and Straboviridae, which showed significantly higher gut abundance among translocated observations (FDR <0.01). IgG reactivity against a specific phage in 90% of investigated individuals was associated with the absence of that phage in the patients virome; at the collective population analysis, IgG reactivity showed a weak negative association with serum phage abundance. These observations suggest antibody-mediated clearance that limits systemic persistence. Together, these findings suggest that rare epithelial passage, lymphatic trafficking, and IgG-mediated neutralization act as sequential filters that limit which gut phages reach and persist in the circulation, with implications for phage therapy delivery and for the dissemination of accessory genetic elements beyond the intestine.

microbiology↗

bioRxiv2023

Identification of cross-reacting IgG hotspots to prevent immune evasion of SARS-CoV-2 variants

The major factor that shapes the global perspective for increase or diminution of successive pandemic waves of COVID-19 is the immunological protection. The SARS-CoV-2 virus constantly develops new variants, and capability of immune evasion is among the major factors that promote variant spreading in the human population. After two years of the pandemic and virus evolution, it is almost impossible to explain effects of all possible combinations different viral strains, a few types of vaccinations or new variants infecting an individual patient. Instead of variant-to-variant comparisons, identification of key protein regions linked to immune evasion could be efficient. Here we report an approach for experimental identification of SARS-CoV-2 protein regions that (i) have characteristics of cross-reacting IgG hot-spots, and (ii) are highly immunogenic. Cross-reacting IgG hot spots are regions of protein frequently recognized in many variants by cross-reacting antibodies. Immunogenic regions efficiently induce specific IgG production in SARS-CoV-2 infected patients. We determined four regions that demonstrate both significant immunogenicity and the activity of a cross-reacting IgG hot-spot in protein S, and two such regions in protein N. Their distribution within the proteins suggests that they may be useful in vaccine design and in serological diagnostics of COVID-19.

immunology↗