A therapeutic Porphyromonas gingivalis gingipain vaccine induces neutralising IgG1 antibodies that protect against experimental periodontitis.

Ivan Darby ,Jackie Mccluskey ,Nada Slakeski,Neil M O'brien-Simpson ,Joseph Holden ,A. M. Brown ,Tony Rowe,Bing Ma,Gail C Brammar,Yan Tan,Andrew Hammet,Andrew D. Nash ,Didier Vingadassalom,Eric C. Reynolds ,William Singleton,Keith J. Cross ,Katrina A Walsh,Harold Kleanthous,Jason C. Lenzo ,Adriana Baz Morelli,Dorit Becher,Rebecca Orth

doi:10.1038/npjvaccines.2016.22

Ivan Darby , Jackie Mccluskey

Open Access

https://doi.org/10.1038/npjvaccines.2016.22

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Abstract

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.

Highlights

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth that is associated with a polymicrobial biofilm accreted to the tooth which results in destruction of the tooth’s supporting tissues including the alveolar bone.[1]
Bacteria-induced bone resorption was determined as described in the Materials and Methods section for each group (n = 12), and the data are expressed as the mean ± standard deviation in mm[2] and were analysed using a one-way ANOVA and Dunnetts T3 post-hoc test. * indicates data that are significantly different (P o0.01) from the data for P. gingivalis or P. gingivalis W50/T. denticola/T. forsythia challenged groups. (b) Serum antibody subclass responses of immunised mice in the multi-pathogen periodontitis model
Antisera was used to probe formalin killed P. gingivalis strain W50 as the absorbed antigen in an ELISA and antibody responses are expressed as the ELISA titre obtained minus double the background level, with each titre representing the mean ± standard deviation of three values. * indicates IgG subclass significantly higher (Po 0.01) than other IgG subclasses in that group. (c) IFNγ and IL-4 producing submandibular lymph node (SMLN) T-cells isolated from each group in the multi-pathogen periodontitis model

Summary

Introduction

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth that is associated with a polymicrobial biofilm (subgingival plaque) accreted to the tooth which results in destruction of the tooth’s supporting tissues including the alveolar bone.[1].

Results

Conclusion