title: Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage.
abstract: We have previously demonstrated that experimental pneumococcal carriage enhances immunity and protects healthy adults against carriage reacquisition after rechallenge with a homologous strain.
  
  
  
  To investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition using a heterologous challenge model.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|2 Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Shaun H
authors.identifier: 0000-0002-7160-6275
authors.initials: SH
authors.lastname: Pennington
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Sherin
authors.initials: S
authors.lastname: Pojar
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Mitsi
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Jenna F
authors.initials: JF
authors.lastname: Gritzfeld
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Elissavet
authors.initials: E
authors.lastname: Nikolaou
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Carla
authors.initials: C
authors.lastname: Solórzano
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Owugha
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Qasim
authors.initials: Q
authors.lastname: Masood
authors.affiliation: 2 Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|3 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi; and.
authors.forename: Melita A
authors.initials: MA
authors.lastname: Gordon
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Angela D
authors.initials: AD
authors.lastname: Wright
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Collins
authors.affiliation: 4 Instituto Butantan, Sao Paulo, Brazil.
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|3 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Queen Elizabeth Central Hospital, Blantyre, Malawi; and.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
authors.affiliation: 1 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Daniela M
authors.identifier: 0000-0002-0594-0902
authors.initials: DM
authors.lastname: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002353:Carrier State / Q000276:immunology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009305:Nasopharynx / Q000276:immunology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D011134:Polysaccharides / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D011134:Polysaccharides
keywords: antibodies; memory B cells; plasma B cells; pneumococcal carriage; pneumococcal polysaccharide