title: Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.
abstract: BACKGROUND
  Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.
  
  
  METHODS
  Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine.
  
  
  RESULTS
  All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.
  
  
  CONCLUSIONS
  Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01123941 NCT01193907.
authors: Center for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.
authors: Pierre
authors: P
authors: van Damme
authors: Froukje
authors: F
authors: Kafeja
authors: Alessandra
authors: A
authors: Anemona
authors: Venere
authors: V
authors: Basile
authors: Anne Katrin
authors: AK
authors: Hilbert
authors: Ilse
authors: I
authors: De Coster
authors: Simona
authors: S
authors: Rondini
authors: Francesca
authors: F
authors: Micoli
authors: Rana M
authors: RM
authors: Qasim Khan
authors: Elisa
authors: E
authors: Marchetti
authors: Vito
authors: V
authors: Di Cioccio
authors: Allan
authors: A
authors: Saul
authors: Laura B
authors: LB
authors: Martin
authors: Audino
authors: A
authors: Podda
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000009:adverse effects* / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D011135:Polysaccharides, Bacterial / Q000009:adverse effects* / Q000276:immunology*; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000009:adverse effects* / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)