Abstract Title:

Hyporesponsiveness following booster immunization with bacterial polysaccharides is caused by apoptosis of memory B cells.

Abstract Source:

J Infect Dis. 2012 Feb ;205(3):422-30. Epub 2011 Dec 7. PMID: 22158565

Abstract Author(s):

Siggeir F Brynjolfsson, Maren Henneken, Stefania P Bjarnarson, Elena Mori, Giuseppe Del Giudice, Ingileif Jonsdottir

Article Affiliation:

Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.


BACKGROUND: Repeated immunizations with polysaccharide (PS) vaccines cause hyporesponsiveness through undefined mechanisms. We assessed the effects of a PS booster on immune responses, frequency, and survival of PS-specific B-cell subpopulations in spleen and bone marrow.

METHODS: Neonatal mice were primed with meningococcus serotype C (MenC) conjugate MenC-CRM(197)+CpG1826, boosted with MenC-CRM(197), MenC-PS, or saline; subsequently, bromodeoxyuridine (BrdU) was injected daily intraperitoneally. MenC-PS-specific cells were labeled with fluorescent MenC-PS and phenotyped by flow cytometry.

RESULTS: After MenC-PS booster, proliferating (BrdU(+)) MenC-PS-specific naive B cells (CD138(-)/B220(+); P = .0003) and plasma cells (CD138(+)/B220(-); P = .0002) in spleen were fewer than after saline booster. BrdU(+) MenC-PS-specific plasma cells were also reduced in bone marrow (P = .0308). Compared to saline, MenC-PS booster reduced BrdU(+) IgG(+) MenC-PS-specific B cells in spleen (P = .0002). Twelve hours after the MenC-PS booster, an increased frequency of apoptotic (AnnexinV(+)) MenC-PS-specific B cells in spleen was observed compared with MenC-CRM(197) (P = .0286) or saline (P = .001) boosters.

CONCLUSIONS: We demonstrated that the MenC-PS booster significantly reduced the frequency of newly activated MenC-PS-specific B cells-mostly switched IgG(+) memory cells-by driving them into apoptosis. It shows directly that apoptosis of PS-specific memory cells is the cause of PS-induced hyporesponsiveness. These results should be taken into account prior to consideration of the use of PS vaccines.

Study Type : Animal Study
Additional Links
Substances : vaccine
Pharmacological Actions : Apoptotic : CK(6986) : AC(5304)
Problem Substances : vaccine
Adverse Pharmacological Actions : Apoptotic : CK(203) : AC(83)

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