title: Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice.
abstract: Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections.
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Qian
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Yi
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, 306 Hospital of People's Liberation Army, Beijing, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Changming
authors.initials: C
authors.lastname: Yu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy / Q000382:microbiology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011485:Protein Binding; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins