Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin B

Larkin, Eileen A.; Stiles, Bradley G.; Ulrich, Robert G.

doi:10.1371/journal.pone.0013253

Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin B

Journal Article · Mon Oct 11 00:00:00 EDT 2010 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0013253· OSTI ID:1627427

Larkin, Eileen A. ^[1]; Stiles, Bradley G. ^[2]; Ulrich, Robert G. ^[3]

Medical Research Institute of Infectious Diseases, Frederick, MD (United States); Hood College, Frederick, MD (United States); DOE/OSTI
Medical Research Institute of Infectious Diseases, Frederick, MD (United States); Wilson College, Chambersburg, PA (United States)
Medical Research Institute of Infectious Diseases, Frederick, MD (United States); Hood College, Frederick, MD (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Hood College, Frederick, MD (United States); Medical Research Institute of Infectious Diseases, Frederick, MD (United States)

Sponsoring Organization:: Joint Science and Technology Office; Medical Research and Materiel Command; USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 1627427

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 10 Vol. 5; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma Haylock, Anna-Karin; Spiegelberg, Diana; Mortensen, Anja C. International Journal of Oncology, Vol. 48, Issue 2 https://doi.org/10.3892/ijo.2015.3290	journal	December 2015
The staphylococcal enterotoxin (SE) family: SEB and siblings Krakauer, Teresa; Stiles, Bradley G. Virulence, Vol. 4, Issue 8 https://doi.org/10.4161/viru.23905	journal	November 2013
Synthetic Human Monoclonal Antibodies toward Staphylococcal Enterotoxin B (SEB) Protective against Toxic Shock Syndrome Karauzum, Hatice; Chen, Gang; Abaandou, Laura Journal of Biological Chemistry, Vol. 287, Issue 30 https://doi.org/10.1074/jbc.m112.364075	journal	May 2012
Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies Dutta, Kaushik; Varshney, Avanish K.; Franklin, Matthew C. Journal of Biological Chemistry, Vol. 290, Issue 11 https://doi.org/10.1074/jbc.m114.630715	journal	March 2015
Engineered pH-dependent recycling antibodies enhance elimination of Staphylococcal enterotoxin B superantigen in mice Kroetsch, Andrew; Qiao, Chunxia; Heavey, Mairead mAbs, Vol. 11, Issue 2 https://doi.org/10.1080/19420862.2018.1545510	journal	December 2018
Therapeutic Treatment of Aerosolized Staphylococcal Enterotoxin B in Nonhuman Primates with two Monoclonal Antibodies Verreault, Daniel; Ennis, Jane; Whaley, Kevin BioRxiv https://doi.org/10.1101/424036	posted_content	January 2018
Isotype Switching Increases Efficacy of Antibody Protection against Staphylococcal Enterotoxin B-Induced Lethal Shock and Staphylococcus aureus Sepsis in Mice Varshney, Avanish K.; Wang, Xiaobo; Aguilar, Jorge L. mBio, Vol. 5, Issue 3 https://doi.org/10.1128/mbio.01007-14	journal	June 2014
Antibodies for biodefense Froude, Jeffrey W.; Stiles, Bradley G.; Pelat, Thibaut mAbs, Vol. 3, Issue 6 https://doi.org/10.4161/mabs.3.6.17621	journal	November 2011

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59 BASIC BIOLOGICAL SCIENCES
T cells
antibodies
antibody therapy
enzyme-linked immunoassays
monoclonal antibodies
staphylococcus aureus
toxic shock syndrome
toxins

Inhibition of Toxic Shock by Human Monoclonal Antibodies against Staphylococcal Enterotoxin B

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