Pseudomonas aeruginosa immunotype 5 polysaccharide-toxin A conjugate vaccine

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Abstract
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 > 670,000. The conjugate was nontoxic for mice and nonpyrogenic at a dose of 50 .mu.g/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 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 .times. 101 P. aeruginosa for control mice to 9.6 .times. 105 P. aeruginosa for vaccinated mice. Similarly, immunization raised the mean lethal dose for toxin A from 0.2 to 4.67 .mu.g per mouse.

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