The adjuvant LT-K63 can restore delayed maturation of follicular dendritic cells and poor persistence of both protein- and polysaccharide-specific antibody-secreting cells in neonatal mice.

2.50
Hdl Handle:
http://hdl.handle.net/2336/249333
Title:
The adjuvant LT-K63 can restore delayed maturation of follicular dendritic cells and poor persistence of both protein- and polysaccharide-specific antibody-secreting cells in neonatal mice.
Authors:
Bjarnarson, Stefania P; Adarna, Brenda C; Benonisson, Hreinn; Del Giudice, Giuseppe; Jonsdottir, Ingileif
Citation:
J. Immunol. 2012, 189(3):1265-73
Issue Date:
1-Aug-2012
Abstract:
Ab responses in early life are low and short-lived; therefore, induction of protective immunity requires repeated vaccinations. One of the major limitations in early-life immunity is delayed maturation of follicular dendritic cells (FDCs), which play a central role in mediating the germinal center (GC) reaction leading to production of Ab-secreting cells (AbSCs). We assessed whether a nontoxic mutant of Escherichia coli heat-labile enterotoxin (LT-K63) and CpG1826 as model adjuvants could accelerate FDC maturation and immune response in neonatal mice, using a pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (Pnc1-TT) as a model vaccine. In neonatal NMRI mice, a single dose of Pnc1-TT coadministered with LT-K63 enhanced Pnc1-TT-induced GC reaction. In contrast, CpG1826 had no effect. Accordingly, LT-K63, but not CpG1826, accelerated the maturation of FDC networks, detected by FDC-M2(+) staining, characteristic for adult-like FDCs. This coincided with migration of MOMA-1(+) macrophages into the GCs that can enhance GC reaction and B cell activation. The FDC-M2(+) FDC networks colocalized with enhanced expression of TNF-α, which is critical for the maintenance of mature FDCs and is poorly expressed in neonates. The accelerated maturation of FDC networks correlated with increased frequency and prolonged persistence of polysaccharide- and protein-specific IgG(+) AbSCs in spleen and bone marrow. Our data show for the first time, to our knowledge, that an adjuvant (LT-K63) can overcome delayed maturation of FDCs in neonates, enhance the GC reaction, and prolong the persistence of vaccine-specific AbSCs in the BM. These properties are attractive for parenteral vaccination in early life.
Description:
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DC FieldValueLanguage
dc.contributor.authorBjarnarson, Stefania Pen_GB
dc.contributor.authorAdarna, Brenda Cen_GB
dc.contributor.authorBenonisson, Hreinnen_GB
dc.contributor.authorDel Giudice, Giuseppeen_GB
dc.contributor.authorJonsdottir, Ingileifen_GB
dc.date.accessioned2012-10-18T11:00:29Z-
dc.date.available2012-10-18T11:00:29Z-
dc.date.issued2012-08-01-
dc.date.submitted2012-10-18-
dc.identifier.citationJ. Immunol. 2012, 189(3):1265-73en_GB
dc.identifier.issn1550-6606-
dc.identifier.pmid22753937-
dc.identifier.doi10.4049/jimmunol.1200761-
dc.identifier.urihttp://hdl.handle.net/2336/249333-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractAb responses in early life are low and short-lived; therefore, induction of protective immunity requires repeated vaccinations. One of the major limitations in early-life immunity is delayed maturation of follicular dendritic cells (FDCs), which play a central role in mediating the germinal center (GC) reaction leading to production of Ab-secreting cells (AbSCs). We assessed whether a nontoxic mutant of Escherichia coli heat-labile enterotoxin (LT-K63) and CpG1826 as model adjuvants could accelerate FDC maturation and immune response in neonatal mice, using a pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (Pnc1-TT) as a model vaccine. In neonatal NMRI mice, a single dose of Pnc1-TT coadministered with LT-K63 enhanced Pnc1-TT-induced GC reaction. In contrast, CpG1826 had no effect. Accordingly, LT-K63, but not CpG1826, accelerated the maturation of FDC networks, detected by FDC-M2(+) staining, characteristic for adult-like FDCs. This coincided with migration of MOMA-1(+) macrophages into the GCs that can enhance GC reaction and B cell activation. The FDC-M2(+) FDC networks colocalized with enhanced expression of TNF-α, which is critical for the maintenance of mature FDCs and is poorly expressed in neonates. The accelerated maturation of FDC networks correlated with increased frequency and prolonged persistence of polysaccharide- and protein-specific IgG(+) AbSCs in spleen and bone marrow. Our data show for the first time, to our knowledge, that an adjuvant (LT-K63) can overcome delayed maturation of FDCs in neonates, enhance the GC reaction, and prolong the persistence of vaccine-specific AbSCs in the BM. These properties are attractive for parenteral vaccination in early life.en_GB
dc.description.sponsorshipIcelandic Research Fund Landspitali University Hospital Research Fund University of Iceland Research Fund European Commission Icelandic Research Fund for Graduate Students Eimskip Fund of the University of Icelanden_GB
dc.language.isoenen
dc.relationhttp://dx.doi.org/10.4049/jimmunol.1200761-
dc.rightsArchived with thanks to Journal of immunology (Baltimore, Md. : 1950)en_GB
dc.subject.meshAdjuvants, Immunologicen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAnimals, Newbornen_GB
dc.subject.meshAntibodies, Bacterialen_GB
dc.subject.meshAntibody-Producing Cellsen_GB
dc.subject.meshBacterial Toxinsen_GB
dc.subject.meshCell Differentiationen_GB
dc.subject.meshCpG Islandsen_GB
dc.subject.meshDendritic Cells, Follicularen_GB
dc.subject.meshEnterotoxinsen_GB
dc.subject.meshEscherichia coli Proteinsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred Strainsen_GB
dc.subject.meshOligodeoxyribonucleotidesen_GB
dc.subject.meshPolysaccharides, Bacterialen_GB
dc.subject.meshTetanus Toxoiden_GB
dc.titleThe adjuvant LT-K63 can restore delayed maturation of follicular dendritic cells and poor persistence of both protein- and polysaccharide-specific antibody-secreting cells in neonatal mice.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Landspitali, The National University Hospital of Iceland, Hringbraut, 101 Reykjavik, Iceland.en_GB
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en_GB
dc.rights.accessLandspitali Access - LSH-aðganguren
dc.type.categoryÓnæmisfræðien_GB

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