A built-in adjuvant-engineered mucosal vaccine against dysbiotic periodontal diseases

Abstract

Periodontitis is associated with a dysbiotic shift in the oral microbiome. Vaccine approaches to prevent microbial shifts from healthy to diseased state in oral biofilms would provide a fundamental therapeutic strategy against periodontitis. Since dental plaque formation is a polymicrobial and multilayered process, vaccines targeting single bacterial species would have limited efficacy in clinical applications. In this study, we developed a divalent mucosal vaccine consisting of a mixture of FlaB-tFomA and Hgp44-FlaB fusion proteins targeting virulence factors of inflammophilic bacteria Fusobacterium nucleatum and Porphyromonas gingivalis, respectively. Introduction of peptide linkers between FlaB and antigen improved the stability and immunogenicity of engineered vaccine antigens. The intranasal immunization of divalent vaccine induced protective immune responses inhibiting alveolar bone loss elicited by F. nucleatum and P. gingivalis infection. The built-in flagellin adjuvant fused to protective antigens enhanced antigen-specific antibody responses and class switch recombination. The divalent vaccine antisera recognized natural forms of surface antigens and reacted with diverse clinical isolates of Fusobacterium subspecies and P. gingivalis. The antisera inhibited F. nucleatum-mediated biofilm formation, co-aggregation of P. gingivalis and Treponema denticola, and P. gingivalis-host cell interactions. Taken together, the built-in adjuvant-engineered mucosal vaccine provides a technological platform for multivalent periodontitis vaccines targeting dysbiotic microbiome.Mucosal Immunology (2019) 12:565-579; https://doi.

Variability in Genomic and Virulent Properties of Porphyromonas gingivalis Strains Isolated From Healthy and Severe Chronic Periodontitis Individuals

“…Therefore, we speculate that its absence in H3 impairs its hemagglutination ability. Variation of comparable magnitude in the hemagglutination ability of P. gingivalis strains has been previously reported in strains with other genetic backgrounds (Shoji et al, 2013; Zhang et al, 2016; Puth et al, 2019). Interestingly, among P. gingivalis hemagglutinins, hagA, hagD , and hagE show >70% identity, while hagB and hagC correspond to unrelated families, sharing 93% identity (Connolly et al, 2017).…”

A stealth adhesion factor contributes to Vibrio vulnificus pathogenicity: Flp pili play roles in host invasion, survival in the blood stream and resistance to complement activation

“…To acquire the confocal microscopic images of biofilm, the biofilm was induced in 4 Well Cell Culture Slide (SPL, cat#30124) for 24 hours and then gently washed once with PBS. The biofilm was then stained with acridine orange and observed by a confocal microscope as previously reported [47]. The samples were observed under a LSM510 confocal microscope (Zeiss, Oberkochen, Germany), and the obtained images were analyzed by using the ZEN 2012 x32 blue software.…”

Biological strategies for the prevention of periodontal disease: Probiotics and vaccines

“…Intranasal immunization of mice with BtA and HB resulted in production of specific antibody responses against F. nucleatum and P. gingivalis , and induced protective immune responses which prevented alveolar bone loss. In addition, the antiserum resulted in inhibition of F. nucleatum biofilm formation and co‐aggregation of P. gingivalis 106 …”

“…Fusobacterium nucleatum has served as a target pathogen for periodontal vaccine development because of its intimate relationship with the growth and survival of P. gingivalis within the dental biofilm. In a recent study, a divalent mucosal vaccine was developed which targeted FlaB‐LK1‐tFoma (BtA) and Hgp44‐LK3‐FlaB (HB), fusion proteins associated with virulence factors of F. nucleatum and P. gingivalis 106 . Intranasal immunization of mice with BtA and HB resulted in production of specific antibody responses against F. nucleatum and P. gingivalis , and induced protective immune responses which prevented alveolar bone loss.…”