Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin B
Open Access
- 11 October 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (10), e13253
- https://doi.org/10.1371/journal.pone.0013253
Abstract
Staphylococcus aureus is implicated in many opportunistic bacterial infections around the world. Rising antibiotic resistance and few alternative methods of treatment are just two looming problems associated with clinical management of S. aureus. Among numerous virulence factors produced by S. aureus, staphylococcal enterotoxin (SE) B is a secreted protein that binds T-cell receptor and major histocompatibility complex class II, potentially causing toxic shock mediated by pathological activation of T cells. Recombinant monoclonal antibodies that target SEB and block receptor interactions can be of therapeutic value. The inhibitory and biophysical properties of ten human monoclonal antibodies, isolated from a recombinant library by panning against SEB vaccine (STEBVax), were examined as bivalent Fabs and native full-length IgG (Mab). The best performing Fabs had binding affinities equal to polyclonal IgG, low nanomolar IC50s against SEB in cell culture assays, and protected mice from SEB-induced toxic shock. The orthologous staphylococcal proteins, SEC1 and SEC2, as well as streptococcal pyrogenic exotoxin C were recognized by several Fabs. Four Fabs against SEB, with the lowest IC50s, were converted into native full-length Mabs. Although SEB-binding kinetics were identical between each Fab and respective Mab, a 250-fold greater inhibition of SEB-induced T-cell activation was observed with two Mabs. Results suggest that these human monoclonal antibodies possess high affinity, target specificity, and toxin neutralization qualities essential for any therapeutic agent.Keywords
This publication has 66 references indexed in Scilit:
- Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric AntibodiesInfection and Immunity, 2010
- Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates against Staphylococcus aureusInfection and Immunity, 2009
- Pathogenesis of Methicillin‐ResistantStaphylococcus aureusInfectionClinical Infectious Diseases, 2008
- One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 casesEuropean Journal of Clinical Microbiology & Infectious Diseases, 2007
- Long-term effects of intravenous immunoglobulin in CIDPClinical Neurophysiology, 2007
- Clinical Trial of Safety and Efficacy of IHN-A21 for the Prevention of Nosocomial Staphylococcal Bloodstream Infection in Premature InfantsThe Journal of Pediatrics, 2007
- Community-associated Methicillin-resistantStaphylococcus aureusIsolates and Healthcare-Associated Infections1Emerging Infectious Diseases, 2007
- A randomized prospective study on the use of 2 g-IVIG or 1 g-IVIG as therapy for Kawasaki diseaseEuropean Journal of Pediatrics, 2006
- Phase II, Randomized, Double-Blind, Multicenter Study Comparing the Safety and Pharmacokinetics of Tefibazumab to Placebo for Treatment of Staphylococcus aureus BacteremiaAntimicrobial Agents and Chemotherapy, 2006
- Isolation of a Human Monoclonal Antibody with Strong Neutralizing Activity against Diphtheria ToxinInfection and Immunity, 2006