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A feasibility study of controlled human infection with Streptococcus pneumoniae in Malawi

Morton, Ben ORCID:, Burr, Sarah, Chikaonda, Tarsizio, Nsomba, Edna, Manda-Taylor, Lucinda, Henrion, Marc, Banda, Ndaziona Peter, Rylance, Jamie ORCID:, Ferreira, Daniela ORCID:, Jambo, Kondwani ORCID: and Gordon, Stephen ORCID: (2021) 'A feasibility study of controlled human infection with Streptococcus pneumoniae in Malawi'. EBioMedicine, Vol 72, p. 103579.

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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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 142 Gram-positive bacteria (General)
QW Microbiology and Immunology > Immunity by Type > QW 563 Local immunity
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 27 Sep 2021 08:57
Last Modified: 27 Sep 2021 08:57


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