Polysaccharide-specific memory B-cells predict protection against experimental human 1 pneumococcal carriage

RATIONALE:

We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition following re-challenge with homologous strain. Here we have used a heterologous challenge model to investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition.

METHODS:

We identified healthy volunteers that were naturally colonised with pneumococcus and, following 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 prior to and 7, 14 and 35 days following experimental pneumococcal inoculation.

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 7 days post inoculation.

CONCLUSIONS:

Our data indicate that naturally acquired polysaccharide-specific memory B-cells, but not levels of circulating IgG at time of pneumococcal exposure, are associated with protection against carriage acquisition.