Hyporesponsiveness Following Booster Immunization With Bacterial Polysaccharides Is Caused by Apoptosis of Memory B Cells

Brynjólfsson, Siggeir F.; Henneken, Maren; Bjarnarson, Stefania P.; Mori, Elena; Giudice, Giuseppe Del; Jónsdóttir, Ingileif

doi:10.1093/infdis/jir750

Cited by 40 publications

(30 citation statements)

References 32 publications

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“…We have shown in our neonatal murine model that meningococcal serogroup C polysaccharide (MenC-PS) also induces hyporesponsiveness in mice primed as neonates with a meningococcal C conjugate. The MenC-PS booster induced increased apoptosis of MenC-PS-specific B cells within 8–12 hours, mostly of switched IgG + memory cells [53]. Interestingly, the Pnc1-TT-induced PPS-1-specific long-lived plasma cells that had already homed to their survival niches in the BM were not affected by the PPS-1 booster s.c. and no significant difference was detected in their frequency 7 to 39 days after the booster.…”

Section: Discussionmentioning

confidence: 95%

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: Discussionmentioning

confidence: 95%

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

et al. 2013

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“…It has been shown that a reduction in memory B-cells, and in particular B1b cells which are important in murine protection against pneumococcal disease, occurs in adults given PPS followed by PCV7, suggesting a mechanism for the limited effectiveness of PPS [35]. Studies in mice have revealed that such polysaccharide-induced hyporesponsiveness was associated with increased apoptosis of polysaccharide-specific B-cells when a booster immunization with a meningococcus serotype C polysaccharide vaccine was used [36]. Examination of the memory B-cell response in this Fijian cohort is currently underway and will provide important information as to the long term impact of this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage

Licciardi

Russell

Balloch

et al. 2014

Vaccine

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The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunisation with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunisation. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2015 April 25. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses. The most frequently carried serotypes were 6B (N=11), 19F (N=14) and 23F (N=23). Significantly lower serotype-specific IgG for 19F, 23F but not 6B post-PPS were detected in infants with homologous serotype carriage prior to PPS compared with non-carriers (N=230). However, OPA levels for 6B and 23F were lower in infants that carried these serotypes. Pneumococcal carriage with 19F or 23F at any time prior to PPS immunisation in infants at 12 months of age who were previously primed with PCV resulted in serotype-specific hyporesponsiveness that persisted until 17 months of age. These results may have implications for the timing of infant vaccine schedules, particularly in high disease burden settings.

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“…Plain polysaccharide vaccines are thought to deplete the B MEM pool by inducing strong BCR cross-linking and driving the terminal differentiation of these cells into PCs, 25 or by inducing apoptosis as demonstrated in neonatal mice primed with MenCCV and boosted with MenCPS. 40 A recent study identified IgM-producing B cells as an important subset in the response to PPV-23 in young adults. 41 When the B cell response was compared between young and elderly adults, elderly participants had fewer IgM positive B cells and an impaired IgM response to vaccination.…”

Section: -Valent Pneumococcal Polysaccharide Vaccine (Ppv-23)mentioning

confidence: 99%

Polysaccharide-specific B cell responses to vaccination in humans

Mitchell

Kelly

Pollard

et al. 2014

Human Vaccines & Immunotherapeutics

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Hyporesponsiveness Following Booster Immunization With Bacterial Polysaccharides Is Caused by Apoptosis of Memory B Cells

Cited by 40 publications

References 32 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

Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage

Polysaccharide-specific B cell responses to vaccination in humans

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