Stx2-specific human monoclonal antibodies protect mice against lethal infection with Escherichia coli expressing Stx2 variants.
Shiga toxin-producing Escherichia coli (STEC) strains are responsible for causing hemolytic-uremic syndrome (HUS), and systemic administration of Shiga toxin (Stx)-specific human monoclonal antibodies (HuMAbs) is considered a promising approach for prevention or treatment of the disease in children. The goal of the present study was to investigate the ability of Stx2-specific HuMAbs to protect against infections with STEC strains that produce Stx2 variants. Dose-response studies on five HuMAbs, using the mouse toxicity model, revealed that only the three directed against the A subunit were protective against Stx2 variants, and 5C12 was the most effective among the three tested. Two HuMAbs directed against the B subunit, while highly effective against Stx2, were ineffective against Stx2 variants. In a streptomycin-treated mouse model, parenteral administration of 5C12 significantly protected mice up to 48 h after oral bacterial challenge. We conclude that 5C12, reactive against the Stx2 A subunit, is an excellent candidate for immunotherapy against HUS and that antibodies directed against the A subunit of Stx2 have broad-spectrum activity that includes Stx2 variants, compared with those directed against the B subunit.
Sheoran
Abhineet S
AS
Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA.
Chapman
Susan
S
Singh
Pradeep
P
Donohue-Rolfe
Arthur
A
Tzipori
Saul
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D009500:Neutralization Tests; D021122:Protein Subunits; D022641:Shiga Toxin 2 / Q000276:immunology* / Q000633:toxicity; D013997:Time Factors
D000911:Antibodies, Monoclonal; D021122:Protein Subunits; D022641:Shiga Toxin 2