Investigational Vaccine for Escherichia coli O157: Phase 1 Study of O157 O-Specific Polysaccharide-Pseudomonas aeruginosa Recombinant Exoprotein A Conjugates in Adults

• Published in: The Journal of infectious diseases Vol. 177; no. 2; pp. 383 - 387
• Main Authors: Konadu, Edward Y., Parke, James C., Tran, Hung T., Bryla, Dolores A., Robbins, John B., Szu, Shousun C.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.02.1998; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; ADP Ribose Transferases; Adult; Antibodies; Antibodies, Bacterial - analysis; Antibodies, Bacterial - immunology; Bacterial Toxins; Bacteriology; Biological and medical sciences; Escherichia coli; Escherichia coli Infections - prevention & control; Escherichia coli O157 - genetics; Escherichia coli O157 - immunology; Exotoxins - genetics; Exotoxins - immunology; Female; Fundamental and applied biological sciences. Psychology; Hemolytic uremic syndrome; Humans; Immunity; Immunoglobulin G - analysis; Immunoglobulin G - immunology; Immunoglobulin M - analysis; Immunoglobulin M - immunology; Infections; Lipopolysaccharides; Major Articles; Male; Microbiology; O Antigens - immunology; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa Exotoxin A; Recombinant Fusion Proteins - immunology; Shiga toxins; Shigella; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Conjugate - adverse effects; Vaccines, Conjugate - immunology; Virulence Factors; Volunteerism; Pseudomonadales; Kidney disease; Human; Urinary system disease; Hemolytic uremic syndrome; Toxicity; Escherichia coli; Hemopathy; Vaccine; Infection; Hemolytic anemia; Immunogenicity; Renal failure; Bacteriosis; Phase I trial; Digestive diseases; Bacteria; Intestinal disease; Pseudomonadaceae; Pseudomonas aeruginosa; Enteritis; Recombinant protein; Enterobacteriaceae
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/514203

Escherichia coli O157 causes severe enteritis and the extraintestinal complication hemolyticuremic 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.