Respiratory FimA-Specific Secretory IgA Antibodies Upregulated by DC-Targeting Nasal Double DNA Adjuvant Are Essential for Elimination of Porphyromonas gingivalis

Abstract

Our previous studies showed that a combination of a DNA plasmid encoding Flt3 ligand (pFL) and CpG oligodeoxynucleotides 1826 (CpG ODN) (FL/CpG) as a nasal adjuvant provoked antigen-specific immune responses. In this study, we investigated the efficacy of a nasal vaccine consisting of FimA as the structural subunit of Porphyromonas gingivalis (P. gingivalis) fimbriae and FL/CpG for the induction of FimA-specific antibody (Ab) responses and their protective roles against nasal and lung infection by P. gingivalis, a keystone pathogen in the etiology of periodontal disease. C57BL/6 mice were nasally immunized with recombinant FimA (rFimA) plus FL/CpG three times at weekly intervals. As a control, mice were given nasal rFimA alone. Nasal washes (NWs) and bronchoalveolar lavage fluid (BALF) of mice given nasal rFimA plus FL/CpG resulted in increased levels of rFimA-specific secretory IgA (SIgA) and IgG Ab responses when compared with those in controls. Significantly increased numbers of CD8- or CD11b-expressing mature-type dendritic cells (DCs) were detected in the respiratory inductive and effector tissues of mice given rFimA plus FL/CpG. Additionally, significantly upregulated Th1/Th2-type cytokine responses by rFimA-stimulated CD4+ T cells were noted in the respiratory effector tissues. When mice were challenged with live P. gingivalis via the nasal route, mice immunized nasally with rFimA plus FL/CpG inhibited P. gingivalis colonization in the nasal cavities and lungs. In contrast, controls failed to show protection. Of interest, when IgA-deficient mice given nasal rFimA plus FL/CpG were challenged with nasal P. gingivalis, the inhibition of bacterial colonization in the respiratory tracts was not seen. Taken together, these results show that nasal FL/CpG effectively enhanced DCs and provided balanced Th1- and Th2-type cytokine response-mediated rFimA-specific IgA protective immunity in the respiratory tract against P. gingivalis. A nasal administration with rFimA and FL/CpG could be a candidate for potent mucosal vaccines for the elimination of inhaled P. gingivalis in periodontal patients.

Pan-Genome Analysis of Oral Bacterial Pathogens to Predict a Potential Novel Multi-Epitopes Vaccine Candidate

“…Innate immune cells such as dendritic cells and adaptive immunity lymphocytes, and monocytes/macrophages localized in periodontium recognize and respond to P. gingivalis through pattern recognition receptors (PRRs), followed by the release of inflammatory cytokines and reactive oxygen species [ 18 ]. As P. gingivalis is an oral pathogen, secretory IgA antibody plays a role as the first line of defense by blocking pathogen adherence to host mucosal surfaces [ 89 ].…”

Development of Nasal Vaccines and the Associated Challenges

“…Nasal immunization of mice with ovalbumin (OVA) along with a plasmid encoding FL (pFL) as the nasal DC-targeting adjuvant reportedly induced OVA-specific SIgA and systemic IgG and IgA Ab responses [ 138 ]. The nasal administration of a combination of DNA plasmids encoding the FLT3 ligand (pFL) and CpG oligodeoxynucleotide 1826 (CpG ODN) (FL/CpG), as the nasal mucosal adjuvant, effectively enhanced the DC responses, balanced the Th1 and Th2 type cellular responses, and provided rFimA-specific IgA-based protection in the respiratory tract against Porphyromonas gingivalis [ 139 ].…”

CpG immunostimulatory oligodeoxynucleotide 1826 as a novel nasal ODN adjuvant enhanced the protective efficacy of the periodontitis gene vaccine in a periodontitis model in SD rats

“…The unmethylated CpG-ODNs are ligands and agonists for human and mouse toll-like receptor 9 (TLR9). When CpG-ODNs served as vaccine adjuvants, they could enhance the induction of vaccine-specific humoral and cellular immune responses [ 19 – 24 ]. For example, Kataoka et al .…”

“…For example, Kataoka et al . showed that nasal CpG-ODN effectively enhanced dendritic cells and supplied balanced rFimA-specific IgA protective immunity against P. gingivalis in the respiratory tract [ 19 ]. Khodadadi et al demonstrated that combined use of CpG-ODN adjuvant enhanced the immune protection and efficacy of a multi-epitope DNA vaccine [ 20 ].…”