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

TLDR

Bacterial pneumonia remains a major threat, and developing new vaccines is urgent, yet traditional trials are slow and expensive, requiring large patient cohorts. The study aimed to evaluate the effect of the 13‑valent pneumococcal conjugate vaccine on colonization using a human challenge model. In a double‑blind randomized trial, 100 adults received PCV or hepatitis A vaccine, were inoculated with 80,000 CFU of Streptococcus pneumoniae 6B, and monitored for 21 days via nasal wash cultures. PCV markedly reduced colonization rate, density, and duration compared to control, demonstrating the model’s safety, cost‑effectiveness, and utility for evaluating vaccine efficacy. Clinical trial registered with 45340436.

Abstract

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.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.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.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).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 with45340436.