{"doi":"10.1101/2023.05.31.543151","title":"Progress toward the development of an effective vaccine for Extraintestinal pathogenic <i>E. coli</i> (ExPEC): The application of the multiple-protein subunits vaccine in different murine models","abstract":"Abstract Extraintestinal pathogenic E. coli (ExPEC) is the primary Gram-negative bacterial pathogen, and the leading cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The emergence and increasing prevalence of multidrug-resistance (MDR) ExPEC strains have led to considerable treatment failures, increased hospitalization rates, morbidity, and mortality. A prophylactic vaccine against ExPEC has the potential to reduce severe infection-related morbidity and mortality, helping to address the escalating antimicrobial resistance (AMR) crisis worldwide. The α-hemolysin (HlyA) is a critical, frequently detected secreted cytotoxic virulence factor in ExPEC, with HlyA-expressing ExPEC strains correlating with increased severity and infection dissemination in clinical levels. In this study, we assessed the protective efficacy of pro-HlyA (the inactive and immature precursor of HlyA) and Dual-Hit (a combination of pro-HlyA and SinH-3, the previously reported immunoglobulin-like domain-3 of the invasin-like autotransporter protein SinH), as ExPEC vaccine candidates. We demonstrated that immunizing mice with pro-HlyA or Dual-Hit significantly reduced bacterial burden and increased survival rates against pandemic ExPEC sequence type strains, ST73 (CFT073) and ST95 (UTI89), in the model of bacteremia and mortality. Both pro-HlyA or Dual-Hit immunizations also provided significant protection against UTI89 colonization in the bladder in the murine UTI model. Furthermore, vaccination with Dual-Hit provided enduring and robust protection against a mixture of ten typical high-virulent sequence types of ExPEC strains, resulting in a promising broad-spectrum vaccine candidate. These findings suggest that pro-HlyA and Dual-Hit might serve as highly effective vaccine targets and highlight the potential of these vaccine candidates for further development and evaluation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":407897,"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":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":465023,"name":"Justin R. Clark","orcid":"0000-0003-1590-6828","position":1,"is_corresponding":false},{"id":676715,"name":"James D. Chang","orcid":"0000-0003-3211-3299","position":2,"is_corresponding":false},{"id":683378,"name":"Jacob J. Zulk","orcid":"0000-0002-3758-5503","position":3,"is_corresponding":false},{"id":1106041,"name":"Dylan M. Chirman","orcid":"0000-0002-7178-6333","position":4,"is_corresponding":false},{"id":687818,"name":"Felipe-Andrés Piedra","orcid":"0000-0002-0100-2919","position":5,"is_corresponding":false},{"id":225239,"name":"Kathryn A. Patras","orcid":"0000-0003-2631-8810","position":6,"is_corresponding":false},{"id":363659,"name":"Anthony W. Maresso","orcid":"0000-0002-4452-3490","position":7,"is_corresponding":false},{"id":465025,"name":"Yikun Xing","orcid":"0000-0002-9778-5507","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T01:21:14.562812Z","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":[]}