Gmd-Antikörper als Impfstoff gegen Staphylococcus aureus einschließlich MRSA – Erste experimentelle Resultate und Entwicklung eines 2-Stage-Revisonsmodell am Tier
Alt V, Kates S, Schnettler R, Schwarz E
Aim: A potential target for a vaccination strategy against Staphylococcus aureus including MRSA is the glucosaminidase (Gmd) subunit of autolysin which is an essential enzyme required for binary fission and biofilm formation. The monoclonal antibody anti-Gmd 1C11 is of interest as it bounds to S. aureus during binary fission. The aim of the study was to evaluate the effect of 1C11 against S. aureus in vitro and in vivo including the development of a clinically relevant 2-stage revision model.
Method: The lytic effect of 1C11 on S. aureus was studied in vitro by Xen29 S. aureus of which 10,000 CFU were incubated without antibody (negative control group), or with 50 microg/ml 1C11. Samples were then prepared for scanning electron microscopy.
For first in vivo testing, mice (n=20) received an intraperitoneal injection of saline or 1 mg of purified 1C11 anti-Gmd antibody 3 days prior to surgical implantation of a transtibial pin containing 500,000 CFUs of Xen29 S. aureus. The mice were imaged to assess in vivo bioluminescent imaging (BLI) on day 0, 3, 5, 7, 10, 14. Furthermore, X-rays were performed after 14 days.
Results: In vitro, the bacteria grew mostly as healthy single cells or small chains in the negative control group. In contrast, addition of anti-Gmd antibody caused large clustering and lysis of the cells. In vivo, absence of a BLI signal in the anti-Gmd animals until day 5 can be observed whereas there is a high BLI signal in the control group. X-rays of the mice in the negative control group obtained on day 14 are shown to illustrate the osteolytic lesion, which was not present in the anti-Gmd treated mouse.
Furthermore, a clinical relevant two-stage rabbit model that mimics the clinical situation of a two-stage proecedure after infected arthroplasty was developed in which the 1C11 antibody will be tested in a next step.
Conclusion: 1C11-anti-Gmd-antibody is a promising antibody for vaccination against S. aureus, including MRSA. If it can provide its effectiveness in the new 2-stage rabbit-model it will be of high interest in the field of total joint arthroplasty.
Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2014). Berlin, 28.-31.10.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocWI59-1273
Published: October 13, 2014
© 2014 Alt et al.
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