title: First human challenge testing of a pneumococcal vaccine. Double-blind randomized controlled trial.
abstract: BACKGROUND
  New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates.
  
  
  OBJECTIVE
  Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization.
  
  
  METHODS
  A total of 100 healthy participants aged 18-50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 μl of Streptococcus pneumoniae (6B) per naris.
  
  
  RESULTS
  Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 48]) compared with control subjects (48% [23 of 48]) (risk ratio, 0.22; confidence interval, 0.09-0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017).
  
  
  CONCLUSIONS
  PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines. Clinical trial registered with
  45340436.
authors.affiliation: 1 Respiratory Research Group, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, United Kingdom.|2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Collins
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.|3 Local Comprehensive Research Network, Northwest Coast, Liverpool, United Kingdom.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Wright
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Elena
authors.initials: E
authors.lastname: Mitsi
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Jenna F
authors.initials: JF
authors.lastname: Gritzfeld
authors.affiliation: 1 Respiratory Research Group, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, United Kingdom.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Hancock
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Shaun H
authors.initials: SH
authors.lastname: Pennington
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Duolao
authors.initials: D
authors.lastname: Wang
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Ben
authors.initials: B
authors.lastname: Morton
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ferreira
authors.affiliation: 2 Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; and.|3 Local Comprehensive Research Network, Northwest Coast, Liverpool, United Kingdom.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D008875:Middle Aged; D022242:Pneumococcal Vaccines; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control*; D018074:Vaccines, Conjugate; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: challenge; colonization; pneumococcus; pneumonia; vaccination