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.

• Published in: The Journal of Immunology
• Main Authors: Bjarnarson, Stefania P, Adarna, Brenda C, Benonisson, Hreinn, Del Giudice, Giuseppe, Jonsdottir, Ingileif
• Other Authors: Department of Immunology, Landspitali, The National University Hospital of Iceland, Hringbraut, 101 Reykjavik, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2012
• Subjects: Adjuvants; Immunologic; Animals; Newborn; Antibodies; Bacterial; Antibody-Producing Cells; Bacterial Toxins; Cell Differentiation; CpG Islands; Dendritic Cells; Follicular; Enterotoxins; Escherichia coli Proteins; Mice; Inbred Strains; Oligodeoxyribonucleotides; Polysaccharides; Tetanus Toxoid; Moma; Iceland
• Online Access: http://hdl.handle.net/2336/249333; https://doi.org/10.4049/jimmunol.1200761

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. 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. Icelandic Research Fund Landspitali University Hospital Research Fund University of Iceland Research Fund European Commission Icelandic Research Fund for Graduate Students Eimskip Fund of the ...