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.
Highlights
Secretory IgA (SIgA) antibody (Ab) is the major isotype at the mucosal surface
Significantly elevated levels of recombinant FimA (rFimA)-specific IgA and IgG Abs were seen in bronchoalveolar lavage fluid (BALF) of mice given nasal rFimA plus Flt3 ligand (FL)/CpG when compared with Ab levels in the controls (Figure 1B)
No IgG3 Ab response against rFimA was detected. These findings show that the nasal pFL and CpG ODN (FL/CpG) system effectively upregulated rFimA-specific Ab responses in both mucosal and systemic immune compartments
Summary
Secretory IgA (SIgA) antibody (Ab) is the major isotype at the mucosal surface. SIgA Abs are mainly secreted as dimeric or polymeric forms and play roles as the first line of defense by neutralizing viruses and toxins as well as by inhibiting bacterial adherence to host mucosal surfaces [1]. An additional unique feature of mucosal immunization is to elicit Ag-specific IgG Ab responses in the systemic compartment [2,3,4,5] Despite these advantages, mucosal immunization requires adjuvants or a delivery system for the induction and regulation of Ag-specific immune responses. Mucosal immunization requires adjuvants or a delivery system for the induction and regulation of Ag-specific immune responses In this regard, we have previously shown that nasal application of a DNA plasmid encoding Flt ligand cDNA (pFL) as a mucosal adjuvant and ovalbumin as an Ag preferentially expands CD8+ CD11c+ dendritic cells (DCs) and subsequently induces IL-4-producing CD4+ T cell-mediated Ag-specific mucosal immune responses [6]. We have shown that the combination of pFL and CpG oligodeoxynucleotides (FL/CpG) as a DC-targeting nasal adjuvant enhances Ag-specific mucosal and systemic immunity with a balanced Th1/Th2-type cytokine response that protects from bacterial and viral infection [7,8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
