Controlled human infection and rechallenge with streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults

Daniela M. Ferreira, Daniel Neill, Mathieu Bangert, Jenna F. Gritzfeld, Nicola Green, Adam K. A. Wright, Shaun H. Pennington, Laura Bricio Moreno, Adriana T. Moreno, Eliane N. Miyaji, Angela D. Wright, Andrea M. Collins, David Goldblatt, Aras Kadioglu, Stephen B. Gordon (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

Rationale: The immunological and protective role of pneumococcal carriage in healthy adults is not known, but high rates of disease and death in the 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 rechallenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of the first carriage episode. Serum and nasal wash antibody responses were measured before and after each challenge.

Measurements and Main Results: A total of 29 subjects were experimentally colonized. No subjects were colonized by experimental rechallenge, 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 postcarriage 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 precarriage sera (30%) or saline (10%).

Conclusions: Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against recolonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies may be important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.
Original languageEnglish
Pages (from-to)855-864
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume187
Issue number8
DOIs
Publication statusPublished - 15 Apr 2013

Fingerprint

Dive into the research topics of 'Controlled human infection and rechallenge with streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults'. Together they form a unique fingerprint.

Cite this