A feasibility study of controlled human infection with Streptococcus pneumoniae in Malawi.
Adult
Antibodies, Bacterial
/ immunology
Carrier State
/ immunology
Feasibility Studies
Female
Humans
Malawi
Male
Nasal Mucosa
/ immunology
Nasopharynx
/ immunology
Pneumococcal Infections
/ immunology
Pneumococcal Vaccines
/ immunology
Serogroup
Streptococcus pneumoniae
/ immunology
Vaccination
/ methods
Vaccine Efficacy
Young Adult
Human infection model
Mucosal inflammation
Nasal
Streptococcus pneumoniae
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
15
06
2021
revised:
18
08
2021
accepted:
02
09
2021
pubmed:
28
9
2021
medline:
8
2
2022
entrez:
27
9
2021
Statut:
ppublish
Résumé
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. 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. 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. 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. None.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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
BACKGROUND
None.
Identifiants
pubmed: 34571365
pii: S2352-3964(21)00372-8
doi: 10.1016/j.ebiom.2021.103579
pmc: PMC8479630
pii:
doi:
Substances chimiques
13-valent pneumococcal vaccine
0
Antibodies, Bacterial
0
Pneumococcal Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103579Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211433/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T008822/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interests.