Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage

Abstract

Rationale: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain.Objectives: To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model. Methods:We identified healthy volunteers that were naturally colonized with pneumococcus and, after clearance of their natural carriage episode, challenged them with a heterologous 6B strain. In another cohort of volunteers we assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and 7, 14, and 35 days after experimental pneumococcal inoculation.Measurements and Main Results: Heterologous challenge with 6B resulted in 50% carriage among volunteers with previous natural pneumococcal carriage. Protection from carriage was associated with a high number of circulating 6BPS IgG-secreting memory B cells at baseline. There were no associations between protection from carriage and baseline levels of 6BPS IgG in serum or nasal wash, PspA-specific, or PspC-specific memory B cells or plasma cells. In volunteers who did not develop carriage, the number of circulating 6BPS memory B cells decreased and the number of 6BPS plasma cells increased postinoculation.Conclusions: Our data indicate that naturally acquired PS-specific memory B cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.

Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine

“…Next, nasal washes were processed as described previously 28,29 . As per the study protocol, pneumococcal detection was performed using (1) conventional culture [28][29][30][31] and (2) qPCR targeting the pneumococcal lytA gene 32 . Nasal lining fluid samples (Nasosorption™, Hunt Developments) for Luminex analysis were collected and stored at −80°C as previously described 33 .…”

Streptococcus pneumoniae: transmission, colonization and invasion

“…Thus, PCV likely is effective because it induces IgG, which is not sensitive to the protease, at levels high enough to reach the mucosal surface and block pneumococcal acquisition. In a model of experimental human colonization with S. pneumoniae , levels of CPS-specific memory B cells correlate with protection from acquisition 27 . Such memory B cells can quickly differentiate into antibody-secreting plasma cells following antigen exposure.…”

“…Moreover, these studies corroborated observations in murine models, demonstrating the protective effect of colonization against reacquisition of the same strain up to 1 year following the first colonization episode 75 . Serotype-specific or strain-specific immunity seems to be required for this protection, as challenge of volunteers following a known natural carriage episode with a strain of a different serotype did not result in increased protection 27 . These infection studies also showed that colonization increases levels of S. pneumoniae-specific CD4 + T memory cells in the blood and lungs in humans 80 .…”

Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

“…Individuals were "carriage positive" if any nasal wash culture following experimental challenge contained S. pneumoniae serotype 6B. Carriage was detected by conventional culture and quantified by serial dilution from nasal washes performed at days 2,7,9 and 29 (antecedent study), and 2,6,9 and 27 (concurrent study) 19,[26][27][28]. For carriers, additional washes occurred at days 14 and 21/22.…”