Helmholtz Zentrum für Infektionsforschung Repository >
Division of Molekulare Strukurbiologie (MOSB) >
RG Rekombinante Proteinexpression (RPEX) >
Publications of the RG Rekombinante Proteinexpression (RPEX) >
Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.
this identifier to cite or link
to this item:
|Title: ||Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.|
|Affiliation: ||Department of General, Visceral, Vascular and Paediatric Surgery, University Clinic of Würzburg, Wuerzburg, Germany. firstname.lastname@example.org|
|Citation: ||Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy. 2011, 55 (1):165-73 Antimicrob. Agents Chemother.|
|Journal: ||Antimicrobial agents and chemotherapy|
|Issue Date: ||Jan-2011 |
|PubMed ID: ||20956605|
|Abstract: ||Staphylococcus aureus is the most common cause of nosocomial infections. Multiple antibiotic resistance and severe clinical outcomes provide a strong rationale for development of immunoglobulin-based strategies. Traditionally, novel immunological approaches against bacterial pathogens involve antibodies directed against cell surface-exposed virulence-associated epitopes or toxins. In this study, we generated a monoclonal antibody targeting the housekeeping protein IsaA, a suggested soluble lytic transglycosylase of S. aureus, and tested its therapeutic efficacy in two experimental mouse infection models. A murine anti-IsaA antibody of the IgG1 subclass (UK-66P) showed the highest binding affinity in Biacore analysis. This antibody recognized all S. aureus strains tested, including hospital-acquired and community-acquired methicillin-resistant S. aureus strains. Therapeutic efficacy in vivo in mice was analyzed using a central venous catheter-related infection model and a sepsis survival model. In both models, anti-IsaA IgG1 conferred protection against staphylococcal infection. Ex vivo, UK-66P activates professional phagocytes and induces highly microbicidal reactive oxygen metabolites in a dose-dependent manner, resulting in bacterial killing. The study provides proof of concept that monoclonal IgG1 antibodies with high affinity to the ubiquitously expressed, single-epitope-targeting IsaA are effective in the treatment of staphylococcal infection in different mouse models. Anti-IsaA antibodies might be a useful component in an antibody-based therapeutic for prophylaxis or adjunctive treatment of human cases of S. aureus infections.|
Fluorescent Antibody Technique, Indirect
|Appears in Collections: ||Publications of the RG Rekombinante Proteinexpression (RPEX)|
|Files in This Item:|
|Lorenz et al_final.pdf||original manuscript||847Kb||Adobe PDF|
|Related articles on PubMed|
A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model.
Kuklin NA, Clark DJ, Secore S, Cook J, Cope LD, McNeely T, Noble L, Brown MJ, Zorman JK, Wang XM, Pancari G, Fan H, Isett K, Burgess B, Bryan J, Brownlow M, George H, Meinz M, Liddell ME, Kelly R, Schultz L, Montgomery D, Onishi J, Losada M, Martin M, Ebert T, Tan CY, Schofield TL, Nagy E, Meineke A, Joyce JG, Kurtz MB, Caulfield MJ, Jansen KU, McClements W, Anderson AS
A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo.
Ebert T, Smith S, Pancari G, Clark D, Hampton R, Secore S, Towne V, Fan H, Wang XM, Wu X, Ernst R, Harvey BR, Finnefrock AC, Wang F, Tan C, Durr E, Cope L, Anderson A, An Z, McNeely T
Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice.
Skurnik D, Merighi M, Grout M, Gadjeva M, Maira-Litran T, Ericsson M, Goldmann DA, Huang SS, Datta R, Lee JC, Pier GB
|See all 146 articles|
This item is licensed under a Creative Commons License
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.