Experimental human pneumococcal carriage

Gritzfeld, Jenna Faye
Experimental human pneumococcal carriage. PhD thesis, University of Liverpool.

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Pneumococcal disease is preceded by nasopharyngeal colonization, which is also the source of transmission. Current pneumococcal conjugate vaccines protect against invasive disease and reduce carriage in children, but are less effective against mucosal disease and have limited serotype coverage. There is an urgent need for new vaccines and colonization has been suggested as an alternative endpoint in vaccine licensure. Experimental human pneumococcal carriage, although potentially risky, offers a way to examine colonization in the context of vaccination. Experimental carriage also allows the investigation of the impact of a pathogen on the immunological complexity and normal microbiota of humans, both of which cannot be done using animal models. We developed a safe and reproducible method of experimental human pneumococcal carriage, described bacteriological and immune factors associated with carriage, and examined the density and duration of experimental carriage. The data presented in this thesis show that experimental human pneumococcal carriage was safe and reproducible. There were important bacteriological differences between pneumococcal strains that affected carriage. Asymptomatic upper respiratory tract viral infection increased both the risk of pneumococcal colonization and the levels of mucosal Factor H, leading to increased colonization density. This model will be useful in further studies of pneumococcal pathogenicity and host protection against carriage and disease. The model may also be used to select vaccine candidates by protective efficacy in blocking experimental carriage.

Item Type: Thesis (PhD)
Additional Information: Date: 2015-03 (completed)
Depositing User: Symplectic Admin
Date Deposited: 06 Aug 2015 07:37
Last Modified: 17 Dec 2022 01:34
DOI: 10.17638/02013340
URI: https://livrepository.liverpool.ac.uk/id/eprint/2013340