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

GIAMMARCO RAPONI, M. CRISTINA GHEZZI, MARIA T. LUN, GIULIO BIGOTTI^*, PIER G. NATALI and CARLO MANCINI

Institute of Microbiology, University of Rome ‘La Sapienza’ Ple Aldo Moro 5, 00185 Rome, *Department of Pathology, Catholic University of Rome ‘S. Cuore', Lg. A. Gemelli, 1 00167 Rome and Immunology Laboratory, ‘Regina Elena’ Cancer Institute, Via delle messi d'oro, Rome, Italy

Corresponding author: Dr G. Raponi.

Received 18 Feb. 1999; revised version accepted 16 Aug. 1999.

Abstract

Murine monoclonal antibodies (MAbs) MT1F and ARM1-4, recognising proteins on the surface of untreated Escherichia coli O6:K^-, protected 100% of mice challenged intraperitoneally with 2 x LD50 of the same strain. MAb MT1F protected 70% of animals challenged with 2 x LD50 of E. coli O111:B4, whereas ARM1-4 gave complete protection. Lower survival was observed in mice given either MAb and challenged with E. coli O128:K^-, with values ranging from 30 to 42%. However, the protection afforded against E. coli O111:B4 and E. coli O128:K^- was significantly improved when the mice were pre-treated with a mixture of the two MAbs. Control mice, pre-treated with unrelated ascitic fluid and challenged with any of the E. coli serotypes, showed 100% mortality and organ histological lesions resembling those of the early stages of septic shock. The mice had high levels of circulating endotoxin and tumour necrosis factor- (TNF-) at 90 min after challenge. In contrast, mice treated with MAbs and surviving the infection displayed moderate histological lesions, enhanced bacterial clearance and lower serum levels of TNF-, despite circulating endotoxin levels that were higher than in the control 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 shock. This occurred in spite of the presence of high levels of circulating endotoxin.

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