Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii.

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Serval ID
serval:BIB_5B99C2BFE32C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii.
Journal
Infection and immunity
Author(s)
Mancini S., Menzi C., Oechslin F., Moreillon P., Entenza J.M.
ISSN
1098-5522 (Electronic)
ISSN-L
0019-9567
Publication state
Published
Issued date
12/2016
Peer-reviewed
Oui
Volume
84
Number
12
Pages
3557-3563
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.

Keywords
Adhesins, Bacterial/genetics, Adhesins, Bacterial/immunology, Adhesins, Bacterial/metabolism, Animals, Antibodies, Bacterial/immunology, Bacterial Vaccines/immunology, Carrier Proteins/genetics, Carrier Proteins/immunology, Carrier Proteins/metabolism, Endocarditis, Bacterial/prevention & control, Female, Gene Expression Regulation, Bacterial, Lactobacillus leichmannii/genetics, Lactobacillus leichmannii/metabolism, Platelet Aggregation/immunology, Rats, Streptococcal Infections/microbiology, Streptococcus gordonii/metabolism
Pubmed
Open Access
Yes
Create date
25/10/2016 18:22
Last modification date
20/08/2019 14:14
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