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Updated: Oct 18, 2025
Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
A feasibility study of controlled human infection with Streptococcus pneumoniae in Malawi
Ben Morton1, Sarah Burr2, Tarsizio Chikaonda3
1Malawi-Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, College of Medicine, P.O. Box 30096, Chichiri, Blantyre, Malawi; Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom; Liverpool University Hospitals NHS Foundation Trust Liverpool L9 7AL, United Kingdom; Queen Elizabeth Central Hospital, P.O. Box 95, Blantyre, Malawi.
Background:
Persistent carriage of pneumococcal vaccine serotypes has occurred after introduction of PCV13 vaccination in Africa but the mechanisms are unclear. We tested the feasibility of using a human pneumococcal challenge model in Malawi to understand immune correlates of protection against carriage and to trial alternative vaccine candidates. We aimed to identify a dose of Streptococcus pneumoniae serotype 6B sufficient to establish nasopharyngeal carriage in 40% of those nasally inoculated and evaluate nasal mucosal immunity before and after experimental inoculation.
Methods:
Healthy student volunteers were recruited and inoculated with saline, 20,000 CFU/naris or 80,000 CFU/naris of Streptococcus pneumoniae serotype 6B Post inoculation carriage was determined by nasal sampling for bacterial culture and lytA PCR. Immunological responses were measured in serum and nasal mucosal biopsies before and after bacterial inoculation.
Findings:
Twenty-four subjects completed the feasibility protocol with minimal side effects. pneumococcal carriage was established in 0/6, 3/9 and 4/9 subjects in the saline, 20,000 CFU/naris and 80,000 CFU/naris groups, respectively. Incidental (natural) serotype carriage was common (7/24 participants carried non-6B strains, 29.2%. Experimentally induced type 6B pneumococcal carriage was associated with pro-inflammatory nasal mucosal responses prior to inoculation and altered mucosal recruitment of immune cells post bacterial challenge. There was no association with serum anti-capsular antibody.
Interpretation:
The serotype 6B experimental human pneumococcal carriage model is feasible in Malawi and can now be used to determine the immunological correlates of protection against carriage and vaccine efficacy in this population.
Funding:
None.
Insights
A new human pneumococcal challenge model in Malawi successfully established Streptococcus pneumoniae serotype 6B carriage. This model will help understand immune responses and test new vaccines against persistent pneumococcal carriage.
Area of Science:
- Infectious Diseases
- Immunology
- Vaccinology
Background:
- Persistent carriage of pneumococcal vaccine serotypes after PCV13 vaccination in Africa remains a challenge, with unclear underlying mechanisms.
- A human pneumococcal challenge model is crucial for understanding immune correlates of protection and evaluating novel vaccine candidates.
Purpose of the Study:
- To establish the feasibility of a human pneumococcal challenge model in Malawi using Streptococcus pneumoniae serotype 6B.
- To identify a dose of serotype 6B sufficient for nasopharyngeal carriage in 40% of inoculated individuals.
- To evaluate changes in nasal mucosal immunity following experimental pneumococcal inoculation.
Main Methods:
- Healthy student volunteers were inoculated with saline, 20,000 CFU/naris, or 80,000 CFU/naris of Streptococcus pneumoniae serotype 6B.
- Nasopharyngeal carriage was assessed via bacterial culture and lytA PCR.
- Serum and nasal mucosal biopsies were analyzed for immunological responses before and after inoculation.
Main Results:
- The experimental model was feasible, with minimal side effects in 24 participants.
- Pneumococcal carriage was established in 44.4% of participants receiving 80,000 CFU/naris.
- Induced carriage correlated with pro-inflammatory nasal responses and altered immune cell recruitment, but not serum antibodies.
Conclusions:
- The experimental human pneumococcal carriage model using serotype 6B is feasible in Malawi.
- This model provides a platform for determining immunological correlates of protection against carriage.
- It will facilitate the evaluation of vaccine efficacy in this population.
