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


OBJECTIVE
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.


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.
Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Daniela M
DM
Ferreira
Daniel R
DR
Neill
Mathieu
M
Bangert
Jenna F
JF
Gritzfeld
Nicola
N
Green
Adam K A
AK
Wright
Shaun H
SH
Pennington
Laura
L
Bricio-Moreno
Laura
L
Bricio Moreno
Adriana T
AT
Moreno
Eliane N
EN
Miyaji
Angela D
AD
Wright
Andrea M
AM
Collins
David
D
Goldblatt
Aras
A
Kadioglu
Stephen B
SB
Gordon
D000281:Administration, Intranasal; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002353:Carrier State / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D017817:Nasal Lavage Fluid / Q000276:immunology / Q000382:microbiology; D009297:Nasal Mucosa / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D055815:Young Adult
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C051592:pneumococcal surface protein A