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.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Bjarnarson, Stefania PAdarna, Brenda C
Benonisson, Hreinn
Del Giudice, Giuseppe
Jonsdottir, Ingileif
Issue Date
2012-08-01
Metadata
Show full item recordCitation
J. Immunol. 2012, 189(3):1265-73Abstract
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
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Rights
Archived with thanks to Journal of immunology (Baltimore, Md. : 1950)ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1200761
Scopus Count
Collections
Related articles
- Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice.
- Authors: Jakobsen H, Bjarnarson S, Del Giudice G, Moreau M, Siegrist CA, Jonsdottir I
- Issue date: 2002 Mar
- Effects of LT-K63 and CpG2006 on phenotype and function of murine neonatal lymphoid cells.
- Authors: Olafsdottir TA, Hannesdottir SG, Giudice GD, Trannoy E, Jonsdottir I
- Issue date: 2007 Oct
- Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice.
- Authors: Aradottir Pind AA, Dubik M, Thorsdottir S, Meinke A, Harandi AM, Holmgren J, Del Giudice G, Jonsdottir I, Bjarnarson SP
- Issue date: 2019
- Neonatal immune response and serum bactericidal activity induced by a meningococcal conjugate vaccine is enhanced by LT-K63 and CpG2006.
- Authors: Brynjolfsson SF, Bjarnarson SP, Mori E, Del Giudice G, Jonsdottir I
- Issue date: 2008 Aug 18
- The advantage of mucosal immunization for polysaccharide-specific memory responses in early life.
- Authors: Bjarnarson SP, Jakobsen H, Del Giudice G, Trannoy E, Siegrist CA, Jonsdottir I
- Issue date: 2005 Apr