Application of vaccine technology to prevention of Pseudomonas aeruginosa infections

Abstract

Development of an effective vaccine against the multiple presentations of Pseudomonas aeruginosa infection, including nosocomial pneumonia, bloodstream infections, chronic lung infections in cystic fibrosis patients and potentially sight-threatening keratitis in users of contact lenses, is a high priority. As with vaccine development for any pathogen, key information about the most effective immunologic effectors of immunity and target antigens needs to be established. For P. aeruginosa, although there is a role for cell-mediated immunity in animals following active vaccination, the bulk of the data indicate that opsonically-active antibodies provide the most effective mediators of acquired immunity. Major target antigens include the lipopolysaccharide O-polysaccharides, cell-surface alginate, flagella, components of the Type III secretion apparatus and outer membrane proteins with a potentially additive effect achieved by including immune effectors to toxins and proteases. A variety of active vaccination approaches have the potential for efficacy such as vaccination with purified or recombinant antigens incorporating multiple epitopes, conjugate vaccines incorporating proteins and carbohydrate antigens, and live attenuated vaccines, including heterologous antigen delivery systems expressing immunogenic P. aeruginosa antigens. A diverse range of passive immunotherapeutic approaches are also candidates for effective immunity, with a variety of human monoclonal antibodies described over the years with good preclinical efficacy and some early Phase I and II studies in humans. Finding an effective active and/or passive vaccination strategy for P. aeruginosa infections could be realized in the next 5 to 10 years, but will require that advances are made in the understanding of antigen expression and immune effectors that work in different human tissues and clinical settings, and also require a means to validate that clinical outcomes achieved in Phase III trials represent meaningful advances in management and treatment of P. aeruginosa infections.

Keywords::

• alginate
• conjugation
• cystic fibrosis
• Pseudomonas aeruginosa
• vaccine
• ventilator-associated pneumonia