Investigational vaccine for Escherichia coli O157: phase 1 study of O157 O-specific polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugates in adults.

Escherichia coli O157 causes severe enteritis and the extraintestinal complication hemolytic-uremic syndrome. Serum IgG against the surface polysaccharide antigen, the O-specific polysaccharide of lipopolysaccharide (LPS), may confer protective immunity by lysing the inocula. In a phase 1 clinical study, three investigational vaccines were studied in 87 healthy adults. The vaccines were prepared by covalently binding E. coli O157 O-specific polysaccharide with Pseudomonas aeruginosa recombinant exoprotein A. No significant reactions were reported. Most volunteers (81%) responded with a > 4-fold increase in IgG LPS antibodies 1 week after vaccination; all volunteers responded with a > 4-fold rise at 4 weeks and this level was sustained for 26 weeks after injection. All three vaccines elicited high titers of serum bactericidal activity that roughly correlated with the serum IgG and IgM LPS antibody levels. A phase 2 study in young children is planned.