Protective features of monoclonal antibodies to Escherichia coli during experimental infection of mice with homologous and heterologous serotypes of E-coli

Murine monoclonal antibodies (MAbs) MT1F and ARM1-4, recognising proteins o n the surface of untreated Escherichia coli O6:K-, protected 100% of mice c hallenged intraperitoneally with 2 x LD50 of the same strain. MAb MT1F prot ected 70% of animals challenged with 2 X LD50 of E. coli O111:B4, whereas A RM1-4 gave complete protection. Lower survival was observed in mice given e ither MAb and challenged with E. coli 0128:K-, with values ranging from 30 to 42%, However, the protection afforded against E. coli O111:B4 and E. col i 0128:K- was significantly improved when the mice were pre-treated with a mixture of the two MAbs, Control mice, pre-treated with unrelated ascitic f luid and challenged with any of the a coli serotypes, showed 100% mortality and organ histological lesions resembling those of the early stages of sep tic shock. The mice had high levels of circulating endotoxin and tumour nec rosis factor-alpha (TNF-alpha) at 90 min after challenge. In contrast, mice treated with MAbs and surviving the infection displayed moderate histologi cal lesions, enhanced bacterial clearance and lower serum levels of TNF-alp ha, despite circulating endotoxin levels that were higher than in the contr ol group. Protection by the MAbs was probably due to the prevention of the bacterial spread to organs and of the cascade of events leading to septic s hock. This occurred in spite of the presence of high levels of circulating endotoxin.