{"doi":"10.3390/vaccines13010095","title":"Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses","abstract":"Background/Objectives: An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. Methods: In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. Results: The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. Conclusions: The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses.","journal":"Vaccines","year":2025,"id":518884,"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":6,"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":669254,"name":"Ekramy E. Sayedahmed","orcid":"0000-0002-4294-6422","position":1,"is_corresponding":false},{"id":1115981,"name":"Marwa Alhashimi","orcid":null,"position":2,"is_corresponding":false},{"id":1115544,"name":"Ahmed Elkashif","orcid":"0000-0001-5207-6718","position":3,"is_corresponding":false},{"id":1387255,"name":"Vivek Gairola","orcid":null,"position":4,"is_corresponding":false},{"id":1387256,"name":"Muralimanohara S. T. Murala","orcid":null,"position":5,"is_corresponding":false},{"id":7179,"name":"Suryaprakash Sambhara","orcid":"0000-0002-4715-5793","position":6,"is_corresponding":false},{"id":669255,"name":"Suresh K. Mittal","orcid":"0000-0001-8475-8449","position":7,"is_corresponding":false},{"id":852421,"name":"Wen-Chien Wang","orcid":"0000-0002-5150-9670","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"39852874","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":[]}