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

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Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Mitsi, Elena, Gritzfeld, Jenna, Nikolaou, Elissavet, SolorzanoGonzalez, Carla, Owugha, Jessica, Masood, Qasim, Gordon, Melita, Wright, Angela, Collins, Andrea ORCID: https://orcid.org/0000-0002-4094-1572, Miyaji, Eliane N, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 and Ferreira, Daniela ORCID: https://orcid.org/0000-0001-7730-9477 (2016) 'Polysaccharide-specific memory B-cells predict protection against experimental human 1 pneumococcal carriage'. American Journal of Respiratory and Critical Care Medicine, Vol 194, Issue 12, pp. 1523-1531.

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Abstract

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.

Item Type: Article
Subjects: QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1164/rccm.201512-2467OC
Depositing User: Kelly Convey
Date Deposited: 21 Jul 2016 10:37
Last Modified: 12 Oct 2018 09:00
URI: http://archive.lstmed.ac.uk/id/eprint/6006

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