First human challenge testing of a pneumococcal vaccine. Double-blind randomized controlled trial.
Collins AM., Wright AD., Mitsi E., Gritzfeld JF., Hancock CA., Pennington SH., Wang D., Morton B., Ferreira DM., Gordon SB.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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