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Controlled Human Infection and Re-Challenge with Streptococcus Pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults.

Ferreira, Daniela ORCID: https://orcid.org/0000-0001-7730-9477, Neill, Daniel R, Bangert, Mathieu, Gritzfeld, Jenna, Green, Nicola, Wright, Adam, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Moreno, Laura Bricio, Moreno, Adriana T, Miyaji, Eliane N, Wright, Angela, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Goldblatt, David, Kadioglu, Aras and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2013) 'Controlled Human Infection and Re-Challenge with Streptococcus Pneumoniae Reveals the Protective Efficacy of Carriage in Healthy Adults.'. American Journal of Respiratory and Critical Care Medicine, Vol 187, Issue 8, pp. 855-864.

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Abstract

RATIONALE: The immunological and protective role of pneumococcal carriage in healthy adults is not known but high rates of disease and death in elderly are associated with low carriage prevalence. OBJECTIVES: We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode. METHODS: Seventy healthy adults were challenged and of those with carriage 10 were re-challenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of first carriage episode. Serum and nasal wash antibody response were measured before and after each challenge. MEASUREMENTS AND MAIN RESULTS: 29 subjects were experimentally colonized. No subjects were colonized by experimental re-challenge demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of post-carriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either pre-carriage sera (30%) or saline (10%). CONCLUSIONS: Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against re-colonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies maybe important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
QW Microbiology and Immunology > Immunity by Type > QW 551 Acquired immunity. Artificial immunity
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified)
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/10.1164/rccm.201212-2277OC
Depositing User: Julie Franco
Date Deposited: 19 Apr 2013 10:56
Last Modified: 12 Oct 2018 08:55
URI: http://archive.lstmed.ac.uk/id/eprint/3333

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