{"doi":"10.1093/jimmun/vkaf283.286","title":"Elicitation of potent neutralizing antibody responses against highly pathogenic avian influenza subtypes H5N1 and H7N9 by sequential vaccination of Indian rhesus macaques 2360","abstract":"Abstract Description Highly pathogenic avian influenza (HPAI) poses an enormous threat to human health and possesses considerable pandemic potential due to the ongoing H5N1 panzootic. HPAI is lethal in humans, with case fatality rates of 40-50%, and an HPAI pandemic could have devastating consequences. To facilitate the development of HPAI vaccination regimens and the isolation of HPAI-neutralizing monoclonal antibodies (mAbs) for prophylactic and therapeutic use, we developed novel mRNA vaccines and adenoviral vectors encoding HPAI hemagglutinins (HAs) and assessed their immunogenicity in three distinct vaccination regimens in six Indian rhesus macaques (RMs). Binding Abs recognizing the H5N1 and H7N9 HAs were detectable in all six RMs following vaccination. Using both HPAI pseudoviruses (PSVs) and live H5N1 virus, we determined that RMs developed HPAI-neutralizing Abs when vaccinated with full-length HA, but not with the HA stem alone. High titers of H5N1-neutralizing Abs were detected in three RMs, with one RM exhibiting peak serum ID50 titers of 1:212,000. HA-specific B cells were readily detectable in vaccinee PBMCs using fluorophore-conjugated HA probes. Our findings provide proof-of-concept for the use of HA-encoding nucleic acid-based vaccines in eliciting high titers of HPAI-neutralizing Abs in primates, and we are currently using our fluorophore-conjugated HA probes to isolate HPAI-neutralizing mAbs for future development as prophylactic and therapeutic agents. Funding Sources This study was funded by startup funds from George Washington University to David I. Watkins and R42 AI155275 (PI: David I. Watkins) from the National Institute of Allergy and Infectious Diseases (NIAID). The funders of this study had no role in its design, data collection and analysis, decision to publish, or manuscript preparation. Topic Categories Vaccines and Immunotherapy (VAC)","journal":"The Journal of Immunology","year":2025,"id":582480,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":432420,"name":"Michael J. Ricciardi","orcid":"0000-0002-8098-8666","position":1,"is_corresponding":false},{"id":1194620,"name":"Jack Mauter","orcid":null,"position":2,"is_corresponding":false},{"id":302909,"name":"Thomas B. Voigt","orcid":"0000-0003-2217-897X","position":3,"is_corresponding":false},{"id":1494546,"name":"Emma L Walker","orcid":null,"position":4,"is_corresponding":false},{"id":819017,"name":"Johan J. Louw","orcid":"0000-0002-4887-858X","position":5,"is_corresponding":false},{"id":1269188,"name":"Noor Ghosh","orcid":null,"position":6,"is_corresponding":false},{"id":1269187,"name":"Christakis Panayiotou","orcid":null,"position":7,"is_corresponding":false},{"id":1003141,"name":"Aaron Yrizarry-Medina","orcid":"0000-0002-2940-7109","position":8,"is_corresponding":false},{"id":1494547,"name":"Giorgio De","orcid":null,"position":9,"is_corresponding":false},{"id":1494548,"name":"Figueiredo Godoy","orcid":null,"position":10,"is_corresponding":false},{"id":1436626,"name":"Jenna N Meanor","orcid":null,"position":11,"is_corresponding":false},{"id":532233,"name":"Matthew R. Reynolds","orcid":"0000-0002-1484-6408","position":12,"is_corresponding":false},{"id":332156,"name":"Dawn M. Dudley","orcid":"0000-0003-0934-2042","position":13,"is_corresponding":false},{"id":286693,"name":"Eva G. Rakasz","orcid":"0000-0001-8197-5309","position":14,"is_corresponding":false},{"id":218442,"name":"Douglas S. Reed","orcid":"0000-0003-0076-9023","position":15,"is_corresponding":false},{"id":531983,"name":"David I. Watkins","orcid":"0000-0003-2826-9661","position":16,"is_corresponding":false},{"id":527089,"name":"Brandon C. Rosen","orcid":"0000-0002-4943-3494","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}