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

Autor:	O'Brien-Simpson NM; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Holden JA; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Lenzo JC; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Tan Y; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Brammar GC; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Walsh KA; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Singleton W; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Orth RKH; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Slakeski N; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Cross KJ; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Darby IB; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia., Becher D; CSL Ltd., Bio21 Institute, Parkville, VIC, Australia., Rowe T; CSL Ltd., Bio21 Institute, Parkville, VIC, Australia., Morelli AB; CSL Ltd., Bio21 Institute, Parkville, VIC, Australia., Hammet A; CSL Ltd., Bio21 Institute, Parkville, VIC, Australia., Nash A; CSL Ltd., Bio21 Institute, Parkville, VIC, Australia., Brown A; Sanofi Pasteur, Cambridge, MA, USA., Ma B; Sanofi Pasteur, Cambridge, MA, USA., Vingadassalom D; Sanofi Pasteur, Cambridge, MA, USA., McCluskey J; Sanofi Pasteur, Cambridge, MA, USA., Kleanthous H; Sanofi Pasteur, Cambridge, MA, USA., Reynolds EC; Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	NPJ vaccines [NPJ Vaccines] 2016 Dec 01; Vol. 1, pp. 16022. Date of Electronic Publication: 2016 Dec 01 (Print Publication: 2016).
DOI:	10.1038/npjvaccines.2016.22
Abstrakt:	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. Competing Interests: D.V., J.M. and H.K. are employees of Sanofi Pasteur; A.B. and B.M. were employees of Sanofi Pasteur during the conduct of the work. T.R., A.B.M., A.H., A.N. are employees of CSL. D.B. was an employee of CSL during the conduct of the work.
Databáze:	MEDLINE
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