title: Safety and vaccine efficacy of an attenuated Vibrio vulnificus strain with deletions in major cytotoxin genes.
abstract: Vibrio vulnificus is a human pathogen causing a rapidly progressing fatal septicemia. We have previously reported that a V. vulnificus large toxin RtxA1 causes programmed necrotic cell death through calcium-mediated mitochondrial dysfunction. Here we developed a live attenuated vaccine strain (CMM781) having deletions in three genes encoding major virulence factors: RTX cytotoxin (rtxA1), hemolysin/cytolysin (vvhA) and metalloprotease (vvpE) of a clinical isolate strain CMCP6. The CMM781 strain showed significant attenuation in cytotoxicity and mouse lethality. The safety of CMM781 was also confirmed by measuring the transepithelial electric resistance of Caco-2 cell monolayers. Intragastric immunization of mice with the live attenuated V. vulnificus strain resulted in induction of systemic and mucosal antibodies specific to the pathogen. Moreover, the vaccinated mice were protected from challenges with high doses of the virulent strain through various injection routes. These results suggest that CMM781 appears to be a safe and effective vaccine candidate that would provide significant protection against V. vulnificus infection.
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun 519-763, Korea College of Pharmacy, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun 519-763, Korea Department of Pharmacology and Dental Therapeutics, Dental Research Institute, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Busung Food and Business, Jangheung, Jeonnam 529-873, Korea.
authors.forename: Jong Ro
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun 519-763, Korea Research Institute of Vibrio Infections and Genome Research Center for Enteropathogenic Bacteria, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun 519-763, Korea Department of Microbiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun 519-763, Korea jhrhee@chonnam.ac.kr.
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D018938:Caco-2 Cells; D003603:Cytotoxins / Q000235:genetics; D006367:HeLa Cells; D006460:Hemolysin Proteins / Q000235:genetics; D006801:Humans; D007928:Lethal Dose 50; D045726:Metalloproteases / Q000172:deficiency / Q000235:genetics; D051379:Mice; D009154:Mutation; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014735:Vibrio Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D041261:Vibrio vulnificus / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D003603:Cytotoxins; D006460:Hemolysin Proteins; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D045726:Metalloproteases
keywords: RtxA1 toxin; Vibrio vulnificus; cytotoxin; live attenuated vaccine