Staphylococcal Enterotoxin B-specific monoclonal antibody 20B1 successfully treats diverse Staphylococcus aureus infections.
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.
Department of Medicine.
Avanish K
AK
Varshney
Xiaobo
X
Wang
Matthew D
MD
Scharff
Jennifer
J
MacIntyre
Richard S
RS
Zollner
Oleg V
OV
Kovalenko
Luis R
LR
Martinez
Fergus R
FR
Byrne
Bettina C
BC
Fries
D000038:Abscess / Q000382:microbiology / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007378:Interleukins / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013207:Staphylococcal Skin Infections; D013209:Staphylococcal Vaccines / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D013848:Thigh / Q000382:microbiology / Q000473:pathology; D014774:Virulence
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D007378:Interleukins; D013209:Staphylococcal Vaccines; D018089:Superantigens; C031818:enterotoxin B, staphylococcal
Staphylococcus aureus; adjunctive therapy; monoclonal antibody; superantigen; virulence