AUTHOR=Kataoka Kosuke , Kawabata Shigetada , Koyanagi Kayo , Hashimoto Yoshiya , Miyake Tatsuro , Fujihashi Kohtaro 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.634923

DOI=10.3389/fimmu.2021.634923

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>) fimbriae and FL/CpG for the induction of FimA-specific antibody (Ab) responses and their protective roles against nasal and lung infection by <italic>P. gingivalis</italic>, a keystone pathogen in the etiology of periodontal disease. C57BL/6 mice were nasally immunized with recombinant FimA (<italic>r</italic>FimA) plus FL/CpG three times at weekly intervals. As a control, mice were given nasal <italic>r</italic>FimA alone. Nasal washes (NWs) and bronchoalveolar lavage fluid (BALF) of mice given nasal <italic>r</italic>FimA plus FL/CpG resulted in increased levels of <italic>r</italic>FimA-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 <italic>r</italic>FimA plus FL/CpG. Additionally, significantly upregulated Th1/Th2-type cytokine responses by <italic>r</italic>FimA-stimulated CD4<sup>+</sup> T cells were noted in the respiratory effector tissues. When mice were challenged with live <italic>P. gingivalis via</italic> the nasal route, mice immunized nasally with <italic>r</italic>FimA plus FL/CpG inhibited <italic>P. gingivalis</italic> colonization in the nasal cavities and lungs. In contrast, controls failed to show protection. Of interest, when IgA-deficient mice given nasal <italic>r</italic>FimA plus FL/CpG were challenged with nasal <italic>P. gingivalis</italic>, 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 <italic>r</italic>FimA-specific IgA protective immunity in the respiratory tract against <italic>P. gingivalis.</italic> A nasal administration with <italic>r</italic>FimA and FL/CpG could be a candidate for potent mucosal vaccines for the elimination of inhaled <italic>P. gingivalis</italic> in periodontal patients.</p>