{"doi":"10.1101/2025.07.13.664638","title":"Low levels of H5N1 HA and NA antibodies in the human population are boosted by seasonal A/H1N1 infection but not by A/H3N2 infection or influenza vaccination","abstract":"ABSTRACT An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus. Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody responses may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556560,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1404177,"name":"Cosette G. Schneider","orcid":"0000-0001-5825-7640","position":1,"is_corresponding":false},{"id":1051027,"name":"Elgin Akin","orcid":"0000-0001-8824-8809","position":2,"is_corresponding":false},{"id":1456223,"name":"Juliahna Hayes","orcid":null,"position":3,"is_corresponding":false},{"id":456503,"name":"Katherine Fenstermacher","orcid":"0000-0003-1139-3711","position":4,"is_corresponding":false},{"id":242115,"name":"Richard E. Rothman","orcid":"0000-0002-1017-9505","position":5,"is_corresponding":false},{"id":234853,"name":"Lynda Coughlan","orcid":"0000-0001-9880-6560","position":6,"is_corresponding":false},{"id":227501,"name":"Andrew Pekosz","orcid":"0000-0003-3248-1761","position":7,"is_corresponding":false},{"id":266887,"name":"Anne P. Werner","orcid":"0000-0003-2322-6830","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:55:08.896385Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}