Octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine

Abstract

An octavalent Pseudomonas aeruginosa conjugate vaccine was synthesized by covalently coupling the O-polysaccharide (O-PS) moiety derived from lipopolysaccharides of Habs serotypes 1, 2, 3, 4, 5, 6, 11 and 12 to toxin A. Adipic acid dihydrazide was used as a spacer molecule to facilitate conjugation. The vaccine was composed of 37% (w/w) O-PS and 63% toxin A, devoid of enzymatic activity characteristic of toxin A, non-toxic for mice and guinea pigs, and non-pyrogenic. The vaccine elicited a significant rise in immunoglobulin G antibody levels to all serotypes of lipopolysaccharide contained in the vaccine and to toxin A. Serotypes 6, 10 and 11 were most immunogenic in mice whereas serotypes 1 and 5 engendered the lowest antibody response. Antitoxin A antibody was able to neutralize the cytotoxicity of toxin A. Immunization of mice with the vaccine conferred significant protection against subsequent challenge with all P. aeruginosa serotype strains contained in the vaccine.