• Am. J. Respir. Crit. Care Med. · Dec 2016

    Polysaccharide-specific Memory B-cells Predict Protection Against Experimental Human Pneumococcal Carriage.

    • Shaun H Pennington, Sherin Pojar, Elena Mitsi, Jenna F Gritzfeld, Elissavet Nikolaou, Carla Solórzano, Jessica T Owugha, Qasim Masood, Melita A Gordon, Angela D Wright, Andrea M Collins, Eliane N Miyaji, Stephen B Gordon, and Daniela M Ferreira.
    • 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
    • Am. J. Respir. Crit. Care Med. 2016 Dec 15; 194 (12): 1523-1531.

    RationaleWe have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain.ObjectivesTo investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model.MethodsWe 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 ResultsHeterologous 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.ConclusionsOur 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.

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