PMID- 26926145 OWN - NLM STAT- MEDLINE DCOM- 20160726 LR - 20190222 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 2 DP - 2016 TI - Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice. PG - e0149460 LID - 10.1371/journal.pone.0149460 [doi] LID - e0149460 AB - 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. FAU - Yang, Yilong AU - Yang Y AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Qian, Mengying AU - Qian M AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Yi, Shaoqiong AU - Yi S AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Liu, Shuling AU - Liu S AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Li, Bing AU - Li B AD - Department of Clinical Laboratory, 306 Hospital of People's Liberation Army, Beijing, PR China. FAU - Yu, Rui AU - Yu R AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Guo, Qiang AU - Guo Q AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Zhang, Xiaopeng AU - Zhang X AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Yu, Changming AU - Yu C AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Li, Jianmin AU - Li J AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Xu, Junjie AU - Xu J AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. FAU - Chen, Wei AU - Chen W AD - Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160229 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-Bacterial Agents) RN - 0 (Antibodies, Monoclonal) RN - 0 (Bacterial Proteins) SB - IM MH - Animals MH - Anti-Bacterial Agents/*pharmacology MH - Antibodies, Monoclonal/immunology/*pharmacology MH - Bacterial Proteins/*antagonists & inhibitors/genetics/immunology/metabolism MH - Blood Platelets/metabolism MH - Disease Models, Animal MH - Female MH - Methicillin-Resistant Staphylococcus aureus/drug effects/immunology MH - Mice MH - Peritonitis/drug therapy/*microbiology MH - Phagocytosis/drug effects/immunology MH - Protein Binding MH - Sepsis/drug therapy/*microbiology MH - Sequence Analysis, DNA MH - Staphylococcal Infections/drug therapy/*microbiology/mortality MH - Staphylococcus aureus/*drug effects/genetics/immunology PMC - PMC4771200 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/03/02 06:00 MHDA- 2016/07/28 06:00 PMCR- 2016/02/29 CRDT- 2016/03/02 06:00 PHST- 2015/12/11 00:00 [received] PHST- 2016/02/01 00:00 [accepted] PHST- 2016/03/02 06:00 [entrez] PHST- 2016/03/02 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] PHST- 2016/02/29 00:00 [pmc-release] AID - PONE-D-15-52013 [pii] AID - 10.1371/journal.pone.0149460 [doi] PST - epublish SO - PLoS One. 2016 Feb 29;11(2):e0149460. doi: 10.1371/journal.pone.0149460. eCollection 2016.