Successful selection of an infection‐protective anti‐Staphylococcus aureus monoclonal antibody and its protective activity in murine infection models
| Autor: | Jumpei Enami, Tadashi Baba, Keiichi Hiramatsu, Hiroyoshi Ohsawa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus medicine.drug_class Immunology Drug Evaluation Preclinical Biology peptidoglycan Monoclonal antibody medicine.disease_cause Microbiology Epitope Sepsis Cell wall chemistry.chemical_compound Mice Virology vaccine medicine Animals Humans Mice Inbred BALB C Antibodies Monoclonal Bacteriology Original Articles Staphylococcal Infections medicine.disease Antibodies Bacterial Disease Models Animal chemistry monoclonal antibody biology.protein Original Article Female Peptidoglycan Antibody Conformational epitope |
| Zdroj: | Microbiology and Immunology |
| ISSN: | 1348-0421 0385-5600 |
| Popis: | Recent clinical trials to develop anti‐methicillin‐resistant Staphylococcus aureus (MRSA) therapeutic antibodies have met unsuccessful sequels. To develop more effective antibodies against MRSA infection, a panel of mAbs against S. aureus cell wall was generated and then screened for the most protective mAb in mouse infection models. Twenty‐two anti‐S. aureus IgG mAbs were obtained from mice that had been immunized with alkali‐processed, deacetylated cell walls of S. aureus. One of these mAbs, ZBIA5H, exhibited life‐saving effects in mouse models of sepsis caused by community‐acquired MRSA strain MW2 and vancomycin‐resistant S. aureus strain VRS1. It also had a curative effect in a MW2‐caused pneumonia model. Curiously, the target of ZBIA5H was considered to be a conformational epitope of either the 1,4‐β‐linkage between N‐acetylmuramic acid and N‐acetyl‐D‐glucosamine or the peptidoglycan per se. Reactivity of ZBIA5H to S. aureus whole cells or purified peptidoglycan was weaker than that of most of the other mAbs generated in this study. However, the latter mAbs did not have the protective activities against S. aureus that ZBIA5H did. These data indicate that the epitopes that trigger production of high‐yield and/or high‐affinity antibodies may not be the most suitable epitopes for developing anti‐infective antibodies. ZBIA5H or its humanized form may find a future clinical application, and its target epitope may be used for the production of vaccines against S. aureus infection. |
| Databáze: | OpenAIRE |
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