Nasal double DNA adjuvant induces salivary FimA-specific secretory IgA antibodies in young and aging mice and blocks Porphyromonas gingivalis binding to a salivary protein

Kenjiro Kobuchi,Tatsuro Miyake,Makoto Umeda,Yoichiro Taguchi,Kosuke Kataoka

doi:10.1186/s12903-019-0886-2

Abstract

BackgroundWe previously showed that nasal administration of a combination of dendritic cell (DC) targeted DNA plasmid expressing Flt3 ligand and CpG oligodeoxynucleotides 1826 as a mucosal adjuvant (double adjuvant, DA) provoked protective immunity in the upper respiratory tract of young adult and aging mice. Here, we investigated whether the nasal DA system induces secretory (S)IgA antibodies (Abs) toward recombinant fimbrillin (rFimA) of Porphyromonas gingivalis (P. gingivalis) in the saliva of young adult and aging mice. Further, we examined the functional applicability of rFimA-specific salivary SIgA Abs.MethodsBALB/c mice (8- or 48-week-old) were nasally immunized with rFimA plus DA three times at weekly intervals. Control mice were nasally administered rFimA alone. Saliva samples were collected 1 week after the final immunization, and were subjected to rFimA-specific ELISA. To examine the functional applicability of rFimA-specific SIgA Abs, IgA-enriched saliva samples were subjected to an inhibition assay in order to assess the numbers of P. gingivalis cells bound to the salivary protein statherin.ResultsThe 8- and 48-week-old mice administered nasal rFimA plus DA showed significantly increased levels of rFimA-specific SIgA Abs in saliva and elevated numbers of CD11c+ DCs in sublingual glands (SLGs), periglandular lymph nodes (PGLNs) and submandibular glands (SMGs) as well as nasopharyngeal-associated lymphoid tissues (NALT) compared to mice administered rFimA alone. Further, rFimA-specific SIgA Abs-containing saliva, in which IgG Abs of 8- and 48-week-old mice administered nasal rFimA plus DA were removed, significantly inhibited binding of P. gingivalis to the salivary protein.ConclusionsThese findings show that this DA system could be an effective nasal vaccine strategy for the enhancement of P. gingivalis-specific protective immunity in the oral cavity of adolescents and older individuals.

Highlights

We previously showed that nasal administration of a combination of dendritic cell (DC) targeted DNA plasmid expressing Flt3 ligand and CpG oligodeoxynucleotides 1826 as a mucosal adjuvant provoked protective immunity in the upper respiratory tract of young adult and aging mice
Nasal immunization with 5 μg of Recombinant FimA (rFimA) plus a combination of plasmid encoding Flt3 ligand cDNA (pFL) and CpG CpG oligodeoxynucleotide 1826 (ODN) resulted in significantly increased levels of salivary rFimA-specific SIgA Ab responses in 8-week-old mice compared to those in identically aged mice given nasal rFimA alone (Fig. 2)
Since our previous studies showed that a combination of pFL and CpG oligodeoxynucleotides (CpG ODN) as nasal adjuvants preferentially expands CD11c+ DCs in mucosal inductive and effector tissues [22, 30], we examined the frequency of CD11c+ DCs in the various mucosal tissues of 8- and 48-week-old mice administered rFimA plus double adjuvant (DA)

Summary

Introduction

We previously showed that nasal administration of a combination of dendritic cell (DC) targeted DNA plasmid expressing Flt ligand and CpG oligodeoxynucleotides 1826 as a mucosal adjuvant (double adjuvant, DA) provoked protective immunity in the upper respiratory tract of young adult and aging mice. We investigated whether the nasal DA system induces secretory (S)IgA antibodies (Abs) toward recombinant fimbrillin (rFimA) of Porphyromonas gingivalis (P. gingivalis) in the saliva of young adult and aging mice. Fimbriae located on the cell surface of P. gingivalis are primarily composed of polymers of FimA protein (fimbrillin), encoded by the gene fimA [6]. It is known as a virulence factor [7], and plays an important role in colonization through its association with host tissues, including salivary proteins, and other bacteria in the oral cavity [8,9,10]. We previously showed that P. gingivalis FimA protein binds and rigidly to salivary statherin, a human salivary protein, in a solid phase system [13]

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Results

Conclusion