title: Vaccination against Staphylococcus aureus experimental endocarditis using recombinant Lactococcus lactis expressing ClfA or FnbpA.
abstract: Staphylococcus aureus is a major cause of serious infections in humans and animals and a vaccine is becoming a necessity. Lactococcus lactis is a non-pathogenic bacterium that can be used as a vector for the delivery of antigens. We investigated the ability of non-living L. lactis heterologously expressing S. aureus clumping factor A (ClfA) and fibronectin-binding protein A (FnbpA), alone or together, to elicit an immune response in rats and protect them from S. aureus experimental infective endocarditis (IE). L. lactis ClfA was used for immunization against S. aureus Newman (expressing ClfA but not FnbpA), while L. lactis ClfA, L. lactis FnbpA, as well as L. lactis ClfA/FnbpA, were used against S. aureus P8 (expressing ClfA and FnbpA). Vaccination of rats with L. lactis ClfA elicited antibodies that inhibited binding of S. aureus Newman to fibrinogen, triggered the production of IL-17A and conferred protection to 13/19 (68%) of the animals from IE (P<0.05). Immunization with L. lactis ClfA, L. lactis FnbpA or L. lactis ClfA/FnbpA also produced antibodies against the target proteins, but these did not prevent binding of S. aureus P8 to fibrinogen or fibronectin and did not protect animals against S. aureus P8 IE. Moreover, immunization with constructs containing FnbpA did not increase IL-17A production. These results indicate that L. lactis is a valuable antigen delivery system able to elicit efficient humoral and cellular responses. However, the most appropriate antigens affording protection against S. aureus IE are yet to be elucidated.
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Tiago Rafael
authors.initials: TR
authors.lastname: Veloso
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mancini
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Marlyse
authors.initials: M
authors.lastname: Giddey
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vouillamoz
authors.affiliation: Department of Intensive Care Medicine, University Hospital Medical Centre (CHUV) and University of Lausanne, CH-1011 Lausanne, Switzerland.
authors.forename: Yok-Ai
authors.initials: YA
authors.lastname: Que
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreillon
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland. Electronic address: jose.entenza@unil.ch.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Entenza
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D003030:Coagulase / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004696:Endocarditis / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics*; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D004337:Drug Carriers; D005353:Fibronectins; D011994:Recombinant Proteins; D013209:Staphylococcal Vaccines; C078635:fibronectin-binding proteins, bacterial
keywords: ClfA; Endocarditis; FnbpA; Lactococcus lactis immunization; Rat; Staphylococcus aureus; Vaccine