Active Lungs & Breathing NIHR-supported project Infection & Immunity

A Phase IV, Experimental Human Pneumococcal Challenge (EHPC) model to investigate Streptococcus pneumoniae Serotype 3 (SPN3) colonisation following PCV15, a Double Blind Randomised Controlled Trial (DBRCT) in healthy participants aged 18 50 years in the UK.

In plain English

AI plain-English summary

Healthy adults will be deliberately infected with a pneumonia-causing bacterium to test whether a new vaccine can stop the bug from taking hold in the nose. The bacterium *Streptococcus pneumoniae* serotype 3 (SPN3) is a major cause of pneumonia and meningitis, but current vaccines do not reliably prevent people from carrying it in their nasal passages. This carriage is how the bacterium spreads from person to person. This trial gives 106 volunteers either the newer vaccine PCV15 or a placebo, then one month later squirts a live, antibiotic-sensitive strain of SPN3 into their nostrils. Researchers will measure how many vaccinated people develop nasal colonisation compared to those on placebo, and track their immune responses over 28 days before clearing the infection with antibiotics. If PCV15 proves superior to placebo at preventing colonisation, it would provide direct evidence that this vaccine can interrupt transmission of a stubborn serotype. That could shift public health strategy—reducing silent carriage in adults might lower infection rates in vulnerable populations, including older people and infants, without relying solely on childhood immunisation. A small exploratory group will also have nasal biopsies before and after vaccination to examine local immune changes, offering clues about why some vaccines fail to block carriage.

View original technical description
This is a Phase IV Double Blind (participant and observer) Placebo Controlled Randomised Controlled Trial (DBRCT) that will assess the superiority of PCV15 against placebo in healthy adults 18-50 years old exposed to an Experimental Human Pneumococcal Challenge (EHPC). Participants will be randomised 1:1 to receive PCV15 or placebo. We estimate a colonisation rate of 60% for the placebo group (84 participants with available endpoints,or up to 106 participants enrolled after adjusting for 20% attrition). One month following randomisation and vaccination with PCV15 or placebo,all participants will be intranasally inoculated with Streptococcus pneumoniae serotype 3 (SPN3). Participants will be inoculated with a pure culture of a well-characterised,fully sequenced amoxicillin-sensitive pneumococcal serotype 3 (Clade Ia,strain LIV014-S3). Follow-up for 28 days will occur in the clinic with assessment of laboratory measures of the acquisition of nasal pneumococcal colonisation and of immune response after which participants will be required to take a 5-day course of antibiotics. Participants will be considered enrolled into the trial at vaccination. Exploratory Nasal Biopsy cohort: From the 106 participants enrolled,5 participants (not included in the primary endpoint sample size) will be asked to consent for a nasal biopsy procedure during screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will not be blinded as only PCV15 will be provided. These participants wil not be inoculated and the study will terminate after the second biopsy visit (28 after vaccination). The study is sponsored by the University of Oxford with two sites: Oxford (Centre for Clinical Vaccinology and Tropical Medicine) and Liverpool (Liverpool School of Tropical Medicine). The Experimental Human Pneumococcal Challenge model is well established on both sites.

Researchers

Maheshi Ramasamy (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

A Phase IV Double Blind Randomised Controlled Trial (DBRCT) to Investigate the Effect of PCV-13 and PPV-23 on Pneumococcal Colonisation Using the Experimental Human Pneumococcal Challenge (EHPC) Model in Healthy Adults
A human challenge study to evaluate innate and adaptive immune responses to a controlled human infection with BCG administered by the intradermal or aerosol inhaled route in healthy, BCG-na ve or historically BCG-vaccinated, UK adult volunteers
Experimental Human Pneumococcal Carriage to determine optimal protection from carriage and mechanisms of mucosal immunisation against disease
Pneumonia Investigation Bundle to Guide Therapy for Hospitalised Community Acquired Pneumonia (PIB CAP Study)
A Phase 3, Randomized, Double-blind, Active Comparator-Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Adults 50 Years of Age or Older

Original classification

Life-saving Vaccines

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.