Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach.

Autor:	Xing Y; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Clark JR; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Chang JD; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Zulk JJ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Chirman DM; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Piedra F-A; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Vaughan EE; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Hernandez Santos HJ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA., Patras KA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA., Maresso AW; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILOR Labs, Vaccine Development Group, Baylor College of Medicine, Houston, Texas, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2024 May 07; Vol. 92 (5), pp. e0044023. Date of Electronic Publication: 2024 Apr 09.
DOI:	10.1128/iai.00440-23
Abstrakt:	Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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