The zwitterionic type I Streptococcus pneumoniae polysaccharide does not induce memory B cell formation in humans

Trück, Johannes; Lazarus, Rajeka; Clutterbuck, Elizabeth A.; Bowman, Jaclyn; Kibwana, Elizabeth; Bateman, Elizabeth; Pollard, Andrew J.

doi:10.1016/j.imbio.2012.05.008

Cited by 17 publications

(13 citation statements)

References 18 publications

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“…However, plain PPS-1 immunization w/wo LT-K63 adjuvant induces no IgG Abs in our neonatal murine model [26]. In agreement with those results, a recent study in humans demonstrated that plain PPS-1 does not elicit memory B cell formation, similar to other PSs [50]. Furthermore, we have shown that a booster s.c. with the non-zwitterionic PPS-19F causes hyporesponsiveness in mice primed with a monovalent pneumococcal conjugate, Pnc19F-TT, reflected in reduced Ab levels compared with a saline administration.…”

Section: Discussionsupporting

confidence: 91%

Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

et al. 2013

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BackgroundPlain 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).MethodsNeonatal 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.ResultsPPS 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.ConclusionsPPS 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.

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Section: Discussionsupporting

confidence: 91%

Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

et al. 2013

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“…27,28 PBMCs were first isolated from whole blood using lymphoprep™ (Axis-Shield Diagnostics) density gradient centrifugation. After a wash step, PBMCs were cultured at a concentration of 2 × 10 5 cells/well in a mixture of SAC (S. aureus Cowan strain, 1:5000, Calbiochem), CpG oligodeoxynucleotide 2006 (1.8 µg/mL, Source Bioscience) and pokeweed mitogen (PWM, 83 ng/ mL, Sigma) for 6 d at 37 °C, 5% CO 2 , and 95% humidity.…”

Section: Pbmc Isolation and Elispotmentioning

confidence: 99%

Effect of cryopreservation of peripheral blood mononuclear cells (PBMCs) on the variability of an antigen-specific memory B cell ELISpot

Trück

Mitchell²,

Thompson

et al. 2014

Human Vaccines & Immunotherapeutics

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“…Polysaccharide A (PSA), which is expressed on the surface of the gram-negative symbiotic bacterium Bacteroides fragilis , is so far the most-studied ZPS. Other ZPSs that have been widely studied include Streptococcus pneumoniae type 1 polysaccharide [15-17] and Staphylococcus aureus type 5 and type 8 polysaccharides [18, 19]. PSA elicits T-cell responses critical to immunologic development [20, 21] and to protection against inflammatory diseases such as inflammatory bowel disease (IBD) [22].…”

Section: Zwitterionic Polysaccharidesmentioning

confidence: 99%

Carbohydrates and T cells: A sweet twosome

Avci

Tsuji

et al. 2013

Seminars in Immunology

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Carbohydrates as T cell-activating antigens have been generating significant interest. For many years, carbohydrates were thought of as T-independent antigens, however, more recent research had demonstrated that mono- or oligosaccharides glycosidically-linked to peptides can be recognized by T cells. T cell recognition of these glycopeptides depends on the structure of both peptide and glycan portions of the antigen. Subsequently, it was discovered that natural killer T cells recognized glycolipids when presented by the antigen presenting molecule CD1d. A transformative insight into glycan-recognition by T cells occurred when zwitterionic polysaccharides were discovered to bind to and be presented by MHCII to CD4+ T cells. Based on this latter observation, the role that carbohydrate epitopes generated from glycoconjugate vaccines had in activating helper T cells was explored and it was found that these epitopes are presented to specific carbohydrate recognizing T cells through a unique mechanism. Here we review the key interactions between carbohydrate antigens and the adaptive immune system at the molecular, cellular and systems levels exploring the significant biological implications in health and disease.

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The zwitterionic type I Streptococcus pneumoniae polysaccharide does not induce memory B cell formation in humans

Cited by 17 publications

References 18 publications

Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

Effect of cryopreservation of peripheral blood mononuclear cells (PBMCs) on the variability of an antigen-specific memory B cell ELISpot

Carbohydrates and T cells: A sweet twosome

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