Pseudomonas aeruginosa immunotype 5 polysaccharide-toxin A conjugate vaccine.
Polysaccharide (PS) derived from Pseudomonas aeruginosa immunotype 5 lipopolysaccharide was covalently coupled to toxin A by reductive amination with adipic acid dihydrazide as a spacer molecule. The resulting PS-toxin A conjugate was composed of 27.5% PS and 72.5% toxin A. The conjugate was composed of heterogeneous high-molecular-weight species, all of which possessed an Mr greater than 670,000. The conjugate was nontoxic for mice and nonpyrogenic at a dose of 50 micrograms/kg of body weight when intravenously administered to rabbits. Immunization of rabbits with the conjugate evoked both an antilipopolysaccharide immunoglobulin G (IgG) and an anti-toxin A IgG response. Anticonjugate IgG was capable of neutralizing the cytotoxic effect of toxin A. Immunization of mice with the conjugate increased the mean lethal dose from 4.5 X 10(1) P. aeruginosa for control mice to 9.6 X 10(5) P. aeruginosa for vaccinated mice. Similarly, immunization raised the mean lethal dose for toxin A from 0.2 to 4.67 micrograms per mouse.
Cryz
S J
SJ
Furer
E
E
Sadoff
J C
JC
Germanier
R
R
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D002056:Burns / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011552:Pseudomonas Infections / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial