期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 194, 期 12, 页码 1523-1531出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201512-2467OC
关键词
pneumococcal carriage; pneumococcal polysaccharide; memory B cells; plasma B cells; antibodies
资金
- Bill and Melinda Gates Foundation
- Medical Research Council
- National Institute for Health Research
- Wellcome Trust [105616/Z/14/Z]
- Wellcome Trust [105616/Z/14/Z] Funding Source: Wellcome Trust
- MRC [MR/K01188X/1, MR/M011569/1] Funding Source: UKRI
- Medical Research Council [MR/K01188X/1, MR/M011569/1] Funding Source: researchfish
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.
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