Staphylococcal enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse staphylococcus aureus infections

Avanish K. Varshney, Xiaobo Wang, Matthew D. Scharff, Jennifer Maclntyre, Richard S. Zollner, Oleg V. Kovalenko, Luis R. Martinez, Fergus R. Byrne, Bettina C. Fries

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background. Methicillin-resistant Staphylococcus aureus (MRSA) has become a major health threat in the United States. Staphylococcal enterotoxin B (SEB) is a potent superantigen that contributes to its virulence. High mortality and frequent failure of therapy despite available antibiotics have stimulated research efforts to develop adjunctive therapies. Methods. Treatment benefits of SEB-specific monoclonal antibody (mAb) 20B1 were investigated in mice in sepsis, superficial skin, and deep-tissue infection models. Results. Mice challenged with a SEB-producing MRSA strain developed fatal sepsis, extensive tissue skin infection, and abscess-forming deep-seeded thigh muscle infection. Animals preimmunized against SEB or treated passively with mAb 20B1 exhibited enhanced survival in the sepsis model, whereas decrease of bacterial burden was observed in the superficial skin and deep-tissue models. mAb 20B1 bound to SEB in the infected tissue and decreased abscess formation and proinflammatory cytokine levels, lymphocyte proliferation, and neutrophil recruitment. Conclusions. mAb 20B1, an SEB-neutralizing mAb, is effective against MRSA infection. mAb 20B1 protects against lethal sepsis and reduces skin tissue invasion and deep-abscess formation. The mAb penetrates well into the abscess and binds to SEB. It affects the outcome of S. aureus infection by modulating the host's proinflammatory immune response.

Original languageEnglish (US)
Pages (from-to)2058-2066
Number of pages9
JournalJournal of Infectious Diseases
Volume208
Issue number12
DOIs
StatePublished - Dec 15 2013

Fingerprint

Staphylococcus aureus
Monoclonal Antibodies
Abscess
Infection
Sepsis
Methicillin-Resistant Staphylococcus aureus
Skin
Superantigens
Neutrophil Infiltration
Thigh
staphylococcal enterotoxin B
Neutralizing Antibodies
Virulence
Lymphocytes
Cytokines
Anti-Bacterial Agents
Muscles
Mortality
Health
Therapeutics

Keywords

  • Adjunctive therapy
  • Monoclonal antibody
  • Staphylococcus aureus
  • Superantigen
  • Virulence

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

Cite this

Staphylococcal enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse staphylococcus aureus infections. / Varshney, Avanish K.; Wang, Xiaobo; Scharff, Matthew D.; Maclntyre, Jennifer; Zollner, Richard S.; Kovalenko, Oleg V.; Martinez, Luis R.; Byrne, Fergus R.; Fries, Bettina C.

In: Journal of Infectious Diseases, Vol. 208, No. 12, 15.12.2013, p. 2058-2066.

Research output: Contribution to journalArticle

Varshney, AK, Wang, X, Scharff, MD, Maclntyre, J, Zollner, RS, Kovalenko, OV, Martinez, LR, Byrne, FR & Fries, BC 2013, 'Staphylococcal enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse staphylococcus aureus infections', Journal of Infectious Diseases, vol. 208, no. 12, pp. 2058-2066. https://doi.org/10.1093/infdis/jit421
Varshney, Avanish K. ; Wang, Xiaobo ; Scharff, Matthew D. ; Maclntyre, Jennifer ; Zollner, Richard S. ; Kovalenko, Oleg V. ; Martinez, Luis R. ; Byrne, Fergus R. ; Fries, Bettina C. / Staphylococcal enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse staphylococcus aureus infections. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 12. pp. 2058-2066.
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