title: Successful selection of an infection-protective anti-Staphylococcus aureus monoclonal antibody and its protective activity in murine infection models.
abstract: 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.
authors: Central Research Laboratory, Zenyaku Kogyo, 2-33-7, Ohizumi-machi, Nerima-ku, Tokyo, 178-0062; Department of Bacteriology, Juntendo University, 2-1-1 Hongo, Bunnkyo-ku, Tokyo, 113-8421, Japan.
authors: Hiroyoshi
authors: H
authors: Ohsawa
authors: Tadashi
authors: T
authors: Baba
authors: Jumpei
authors: J
authors: Enami
authors: Keiichi
authors: K
authors: Hiramatsu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal
keywords: Staphylococcus aureus; monoclonal antibody; peptidoglycan; vaccine