Polysaccharide-specific memory B cells predict protection against experimental human pneumococcal carriage

SH Pennington, S Pojar, E Mitsi, JF Gritzfeld… - American journal of …, 2016 - atsjournals.org
SH Pennington, S Pojar, E Mitsi, JF Gritzfeld, E Nikolaou, C Solorzano, JT Owugha…
American journal of respiratory and critical care medicine, 2016atsjournals.org
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 …
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.
ATS Journals