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Experimental Human Pneumococcal Carriage

Gritzfeld, Jenna, Wright, Angela, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Wright, Adam K A, Kadioglu, Aras, Ferreira, Daniela ORCID: https://orcid.org/0000-0001-7730-9477 and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2013) 'Experimental Human Pneumococcal Carriage'. Journal of Visualized Experiments (JoVE), Vol 72, Issue e50115.

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Official URL: http://www.jove.com

Abstract

Experimental human pneumococcal carriage (EHPC) is scientifically important because nasopharyngeal carriage of Streptococcus pneumoniae is both the major source of transmission and the prerequisite of invasive disease. A model of carriage will allow accurate determination of the immunological correlates of protection, the immunizing effect of carriage and the effect of host pressure on the pathogen in the nasopharyngeal niche. Further, methods of carriage detection useful in epidemiologic studies, including vaccine studies, can be compared. Aim We aim to develop an EHPC platform that is a safe and useful reproducible method that could be used to down-select candidate novel pneumococcal vaccines with prevention of carriage as a surrogate of vaccine induced immunity. It will work towards testing of candidate vaccines and descriptions of the mechanisms underlying EHPC and vaccine protection from carriage(1). Current conjugate vaccines against pneumococcus protect children from invasive disease although new vaccines are urgently needed as the current vaccine does not confer optimal protection against non-bacteraemic pneumonia and there has been evidence of serotype replacement with non-vaccine serotypes(2-4). Method We inoculate with S. pneumoniae suspended in 100 μl of saline. Safety is a major factor in the development of the EHPC model and is achieved through intensive volunteer screening and monitoring. A safety committee consisting of clinicians and scientists that are independent from the study provides objective feedback on a weekly basis. The bacterial inoculum is standardized and requires that no animal products are inoculated into volunteers (vegetable-based media and saline). The doses required for colonization (10(4)-10(5)) are much lower than those used in animal models (10(7))(5). Detecting pneumococcal carriage is enhanced by a high volume (ideally >10 ml) nasal wash that is relatively mucus free. This protocol will deal with the most important parts of the protocol in turn. These are (a) volunteer selection, (b) pneumococcal inoculum preparation, (c) inoculation, (d) follow-up and (e) carriage detection. Results Our current protocol has been safe in over 100 volunteers at a range of doses using two different bacterial serotypes(6). A dose ranging study using S. pneumoniae 6B and 23F is currently being conducted to determine the optimal inoculation dose for 50% carriage. A predicted 50% rate of carriage will allow the EHPC model to have high sensitivity for vaccine efficacy with small study numbers.

Item Type: Article
Additional Information: JoVE is a peer reviewed, PubMed indexed journal devoted to the publication of biological, medical, chemical and physical research in a video format. This article is accompanied by a video showing how the experiment was conducted.
Subjects: QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.3791/50115
Depositing User: Julie Franco
Date Deposited: 19 Apr 2013 11:01
Last Modified: 12 Oct 2018 08:53
URI: http://archive.lstmed.ac.uk/id/eprint/3339

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