title: Safety, immunogenicity and dose response of VLA84, a new vaccine candidate against Clostridium difficile, in healthy volunteers.
abstract: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea and colitis and the most common pathogen of health care-associated infections. In the US, CDI causes approximately half a million infections and close to 30,000 deaths. Despite antibiotic treatment of C. difficile associated diarrhoea, the disease is complicated by its recurrence in up to 30% of patients.
  
  
  
  An open-label, partially randomized, dose-escalation Phase I trial was performed in two parts. Sixty volunteers aged ≥18 to <65 years were randomized into five treatment groups to receive three immunizations (Day 0, 7, 21) of VLA84 (20μg with Alum, 75μg with or without Alum, 200μg with or without Alum). Eighty-one volunteers aged ≥65 were randomized into four treatment groups (75μg with or without Alum, 200μg with or without Alum) and received four immunizations (Day 0, 7, 28 and 56). All subjects were followed for safety and immunogenicity for six months.
  
  
  
  VLA84 was safe and well tolerated. Fifty-one adult volunteers (85%) and 50 elderly (62%) experienced at least one solicited or unsolicited adverse event (AE). Forty-eight adult volunteers (80%) and 40 elderly (49%) experienced related AEs which were mostly mild or moderate. No related serious adverse event and no death occurred. The vaccine induced high antibody titres against Toxin A and Toxin B in both study populations.
  
  
  
  VLA84 was safe, well tolerated and highly immunogenic in adult volunteers aged ≥18 to <65 years and elderly volunteers aged ≥65 years. This study is registered at ClinicalTrials.gov under registration number NCT01296386.
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bézay
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ayad
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Dubischar
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Firbas
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Hochreiter
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Kiermayr
authors.affiliation: St. Imre University Teaching Hospital, Department of Nephrology-Hypertension and Clinical Pharmacology, Tetenyi St. 12-16, 1115 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kiss
authors.affiliation: Privatklinik Leech, Hugo-Wolf-Gasse 2-4, 8010 Graz, Austria.
authors.forename: Fritz
authors.initials: F
authors.lastname: Pinl
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: bernd.jilma@meduniwien.ac.at.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, 1030 Vienna, Austria.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Westritschnig
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000534:Alum Compounds / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000517:prevention & control*; D003967:Diarrhea / Q000139:chemically induced; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D011994:Recombinant Proteins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; C041524:aluminum sulfate
keywords: C. difficile; C. difficile associated diarrhoea (CDAD); C. difficile infection (CDI); C. difficile vaccine