A therapeutic Porphyromonas gingivalis gingipain vaccine induces neutralising IgG1 antibodies that protect against experimental periodontitis.
Neil M O'Brien-SimpsonJames A HoldenJason C LenzoYan TanGail C BrammarKatrina A WalshWilliam SingletonRebecca K H OrthNada SlakeskiKeith J CrossIvan B DarbyDorit BecherTony RoweAdriana Baz MorelliAndrew HammetAndrew NashAnna BrownBing MaDidier VingadassalomJacqueline McCluskeyHarold KleanthousEric C ReynoldsPublished in: NPJ vaccines (2016)
Porphyromonas gingivalis infected mice with an established P. gingivalis-specific inflammatory immune response were protected from developing alveolar bone resorption by therapeutic vaccination with a chimera (KAS2-A1) immunogen targeting the major virulence factors of the bacterium, the gingipain proteinases. Protection was characterised by an antigen-specific IgG1 isotype antibody and Th2 cell response. Adoptive transfer of KAS2-A1-specific IgG1 or IgG2 expressing B cells confirmed that IgG1-mediated protection. Furthermore, parenteral or intraoral administration of KAS2-A1-specific polyclonal antibodies protected against the development of P. gingivalis-induced bone resorption. The KAS2-A1-specific antibodies neutralised the gingipains by inhibiting: proteolytic activity, binding to host cells/proteins and co-aggregation with other periodontal bacteria. Combining key gingipain sequences into a chimera vaccine produced an effective therapeutic intervention that protected against P. gingivalis-induced periodontitis.
Keyphrases
- immune response
- randomized controlled trial
- cell therapy
- induced apoptosis
- high glucose
- escherichia coli
- bone loss
- signaling pathway
- single cell
- oxidative stress
- biofilm formation
- type diabetes
- bone marrow
- cell death
- mesenchymal stem cells
- soft tissue
- cancer therapy
- endothelial cells
- inflammatory response
- body composition