Determining the immunological characteristics of a novel human monoclonal antibody developed against staphylococcal enterotoxin B
- 10 April 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Human Vaccines & Immunotherapeutics
- Vol. 16 (7), 1708-1718
- https://doi.org/10.1080/21645515.2020.1744362
Abstract
Staphylococci are the main cause of nosocomial infections globally. The exotoxin staphylococcal enterotoxin B (SEB) produced by methicillin-resistant Staphylococcus aureus is a major cause of pathology after a staphylococcal infection. We previously isolated an anti-SEB human monoclonal antibody designated as M0313. Here we further characterize this antibody in vitro and in vivo. Immunoblotting analysis and ELISA results indicated that M0313 accurately recognized and bound to SEB. Its binding affinity to native SEB was measured at the low nM level. M0313 effectively inhibited SEB from inducing mouse splenic lymphocyte and human peripheral blood mononuclear cell proliferation and cytokine release in cell culture. M0313 also neutralized SEB toxicity in BALB/c female mice. Most importantly, M0313 promoted the survival of mice treated with SEB-expressing bacteria. In-vivo imaging revealed that M0313 treatment significantly reduced the replication of SEB-expressing bacteria in mice. The neutralization capacity of M0313 correlated with its ability to block SEB from binding to major histocompatibility complex II and T-cell receptor by binding to the SEB residues 85–102 and 90–92. Thus, the monoclonal antibody M0313 may be developed into a therapeutic agent.Keywords
Funding Information
- the key project of innovative drug development (2015ZX09101033)
- the key project of innovative drug development (2016ZX09J16102-002)
- The National Natural Science Foundation of China (31370932)
This publication has 52 references indexed in Scilit:
- Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEBPLOS ONE, 2011
- Generation, Characterization, and Epitope Mapping of Neutralizing and Protective Monoclonal Antibodies against Staphylococcal Enterotoxin B-induced Lethal ShockOnline Journal of Public Health Informatics, 2011
- Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin BPLOS ONE, 2010
- Staphylococcal EnterotoxinsToxins, 2010
- Oral Vaccine Formulations Stimulate Mucosal and Systemic Antibody Responses against Staphylococcal Enterotoxin B in a Piglet ModelClinical and Vaccine Immunology, 2010
- Proinflammatory Mediators of Toxic Shock and Their Correlation to LethalityMediators of Inflammation, 2010
- Waves of resistance: Staphylococcus aureus in the antibiotic eraNature Reviews Microbiology, 2009
- High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodiesJournal of Virological Methods, 2009
- Central roles for IL-2 and MCP-1 following intranasal exposure to SEB: A new mouse modelResearch in Veterinary Science, 2009
- Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 Å resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptorsJournal of Molecular Biology, 1998