Pneumococcal polysaccharide abrogates conjugate-induced germinal center reaction and depletes antibody secreting cell pool, causing hyporesponsiveness.

• Published in: PLoS ONE
• Main Authors: Bjarnarson, Stefania P, Benonisson, Hreinn, Del Giudice, Giuseppe, Jonsdottir, Ingileif
• Other Authors: Natl Univ Hosp Iceland, Landspitali, Dept Immunol, Reykjavik, Iceland, Univ Iceland, Fac Med, Reykjavik, Iceland, Novartis Vaccines & Diagnost, Siena, Italy, DeCODE Genet, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library Science 2013
• Subjects: Sýkingar; Bólusetningar; Lungnabólga; Tilraunir á dýrum; Animals; Antibody-Producing Cells; Bone Marrow; Enzyme-Linked Immunosorbent Assay; Germinal Center; Immunohistochemistry; Mice; Pneumococcal Vaccines; Spleen; Streptococcus pneumoniae; Iceland
• Online Access: http://hdl.handle.net/2336/317070; https://doi.org/10.1371/journal.pone.0072588

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM). Neonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM(+), IgG(+) follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated. PPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG(+) AbSCs in BM. PPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG(+) AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered. Icelandic Research Fund for Graduate Students/ 50940005, Icelandic Research Fund/40438021-23, Eimskip University Fund, University of Iceland Research Fund, Landspitali University Hospital Research Fund