First Human Challenge Testing of a Pneumococcal Vaccine - Double Blind Randomised Controlled Trial

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 colonisation have been proposed as a novel method to down select between vaccine candidates.

Objectives

Using our safe and reproducible experimental human pneumococcal colonisation model we aimed to determine the effect 13-valent Pneumococcal Conjugate Vaccine (PCV) on colonisation.

Methods and Measurements

100 healthy participants aged 18-50yrs were recruited into this double blind randomised placebo-controlled trial. They were randomly assigned to PCV (n=49) or hepatitis A (control, n=50) vaccination and inoculated with 80,000CFU/100µl of Streptococcus pneumoniae (6B) per naris. Participants were followed up for 21 days to determine pneumococcal colonisation by culture of nasal wash. Main Results: The PCV group had a significantly reduced rate of 6B colonisation - 10% (5/48) compared to control - 48% (23/48) [Risk Ratio 0.22, CI 0.09 to 0.52, p<0.001]. Density of colonisation was reduced in the PCV group compared to the control group following inoculation. The area under the curve (density versus day) was significantly reduced in the PCV compared to control group (geometric mean 259 vs 11183 p=0.017).

Conclusions

PCV reduced pneumococcal colonisation rate, density and duration in healthy adults. The experimental human pneumococcal colonisation model is a safe, cost-effective and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonisation; PCV provides a ‘gold standard’ against which to test these novel vaccines.