Pseudomonas aeruginosa Polysaccharide-Tetanus Toxoid Conjugate Vaccine: Safety and Immunogenicity in Humans

A Pseudomonas aeruginosa polysaccharide-tetanus toxoid (Ttxd) conjugate vaccine was produced. Polysaccharide was derived from lipopolysaccharide (LPS) and covalently linked to Ttxd by using carbodiimide with adipic acid dihydrazide as a spacer molecule. The conjugate possessed a relative molecular weight of ^50,000 and was nontoxic and nonpyrogenic. The vaccine bound serospecific monoclonal antibodies with an avidity similar to LPS and reacted with murine and human opsonic antibody. The vaccine was immunogenic in rabbits and mice and elicited IgG antibody to both LPS and Ttxd. The vaccine was safe when parenterally administered to humans and evoked only mild, transient reactions. Mean titers of IgG antibody to LPS rose 19-fold after immunization, with 82^0 of the volunteers responding with a fourfold or greater rise in titer. IgG antibody to LPS evoked after immunization was opsonic and highly effective at preventing fatal experimental burn wound sepsis due to P. aeruginosa. Human immunity to Pseudomonas aeruginosa has been correlated with humoral antibody to typespecific lipopolysaccharide (LPS) or toxin A [1, 2]. The protective capacity of antibody to LPS has been most-thoroughly studied. Antibody to LPS has been shown to be highly protective against P. aeruginosa infections in a variety of animal model systems [3-5]. Furthermore, clinical evaluation of an LPS-based polyvalent vaccine has yielded promising but inconclusive results [6].