Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii
| Autor: | Frank Oechslin, José M. Entenza, Stefano Mancini, Philippe Moreillon, Carmen Menzi |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lactobacillus casei Platelet Aggregation Immunology Hemagglutinins Viral Microbiology Pathogenesis 03 medical and health sciences Lactobacillus leichmannii Streptococcal Infections medicine Animals Endocarditis Adhesins Bacterial biology Lactococcus lactis Streptococcus gordonii Endocarditis Bacterial Gene Expression Regulation Bacterial medicine.disease biology.organism_classification Antibodies Bacterial Rats Bacterial adhesin body regions 030104 developmental biology Infectious Diseases Bacterial Vaccines Microbial Immunity and Vaccines biology.protein Female Parasitology Adhesins Bacterial/genetics Adhesins Bacterial/immunology Adhesins Bacterial/metabolism Antibodies Bacterial/immunology Bacterial Vaccines/immunology Carrier Proteins/genetics Carrier Proteins/immunology Carrier Proteins/metabolism Endocarditis Bacterial/prevention & control Lactobacillus leichmannii/genetics Lactobacillus leichmannii/metabolism Platelet Aggregation/immunology Streptococcal Infections/microbiology Streptococcus gordonii/metabolism Antibody Carrier Proteins Binding domain |
| Zdroj: | Infection and immunity, vol. 84, no. 12, pp. 3557-3563 |
| Popis: | Streptococcus gordonii and related species of oral viridans group streptococci (VGS) are common etiological agents of infective endocarditis (IE). We explored vaccination as a strategy to prevent VGS-IE, using a novel antigen-presenting system based on non-genetically modified Lactococcus lactis displaying vaccinogens on its surface. Hsa and PadA are surface-located S. gordonii proteins implicated in platelet adhesion and aggregation, which are key steps in the pathogenesis of IE. This function makes them ideal targets for vaccination against VGS-IE. In the present study, we report the use of nonliving L. lactis displaying at its surface the N-terminal region of Hsa or PadA by means of the cell wall binding domain of Lactobacillus casei A2 phage lysine LysA2 (Hsa-LysA2 and PadA-LysA2, respectively) and investigation of their ability to elicit antibodies in rats and to protect them from S. gordonii experimental IE. Immunized and control animals with catheter-induced sterile aortic valve vegetations were inoculated with 10 6 CFU of S. gordonii . The presence of IE was evaluated 24 h later. Immunization of rats with L. lactis Hsa-LysA2, L. lactis PadA-LysA2, or both protected 6/11 (55%), 6/11 (55%), and 11/12 (91%) animals, respectively, from S. gordonii IE ( P < 0.05 versus controls). Protection correlated with the induction of high levels of functional antibodies against both Hsa and PadA that delayed or totally inhibited platelet aggregation by S. gordonii . These results support the value of L. lactis as a system for antigen delivery and of Hsa and PadA as promising candidates for a vaccine against VGS-IE. |
| Databáze: | OpenAIRE |
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