Safety and immunogenicity of Escherichia coli O18 O-specific polysaccharide (O-PS)-toxin A and O-PS-cholera toxin conjugate vaccines in humans.
O-specific polysaccharide (O-PS) isolated from serotype 18 Escherichia coli lipopolysaccharide (LPS) was covalently coupled to either Pseudomonas aeruginosa toxin A (TA) or or cholera toxin (CT). The conjugates were nontoxic and nonpyrogenic. The conjugates were well tolerated on parenteral administration to human volunteers, with only mild, transient local reactions reported. Immunization engendered an IgG antibody response to both the O-PS and carrier protein. Anti-LPS antibody promoted the uptake and killing of an E. coli O18 strain bearing the K1 capsule by human polymorphonuclear leukocytes, which was complement dependent. Antibody to carrier protein neutralized the activity of native TA or CT in cell culture assays. Passively transferred IgG isolated from the serum of immunized donors provided a significant (P less than .01) degree of protection against fatal experimental E. coli O18 sepsis in mice. This study illustrates the potential use of such conjugates as vaccines against E. coli extraintestinal infections.
Cryz
S J
SJ
Swiss Serum and Vaccine Institute, Bern.
Cross
A S
AS
Sadoff
J C
JC
Wegmann
A
A
Que
J U
JU
Fürer
E
E
D036002:ADP Ribose Transferases; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology*; D002772:Cholera Toxin / Q000009:adverse effects / Q000276:immunology*; D022121:Cholera Vaccines; D004926:Escherichia coli / Q000276:immunology*; D005098:Exotoxins / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects; D008297:Male; D051379:Mice; D019081:O Antigens; D011550:Pseudomonas aeruginosa; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D002772:Cholera Toxin; D022121:Cholera Vaccines; D005098:Exotoxins; D019081:O Antigens; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C068569:E coli O18 O-specific polysaccharide-cholera toxin; C068568:E coli O18 O-specific polysaccharide-toxin A