Promises and pitfalls of Pseudomonas aeruginosa lipopolysaccharide as a vaccine antigen.
Antibodies directed to the Pseudomonas aeruginosa lipopolysaccharide (LPS) O-antigens have clearly shown to mediate the most effective immunity to infection caused by LPS-smooth strains. Such strains are major causes of disease in immunocompromised hosts such as burn or cancer patients, individuals in intensive care units, and those who utilize extended-wear contact lenses. Yet producing an effective vaccine composed of non-toxic, immunogenic polysaccharides has been challenging. The chemical diversity among the different O-antigens representative of the 20 major serotypes, plus additional diversity among some O-antigens representing variant subtype antigens, translates into a large degree of serologic variability that increases the complexity of O-antigen specific vaccines. Further complications come from the poor immunogenicity of the major protective epitope expressed by some O-antigens, and a large degree of diversity in animal responses that preclude predicting the optimal vaccine formulation from such studies. Nonetheless human trials over the years of vaccines eliciting O-antigen immunity have been encouraging, though no vaccine has yet been fully evaluated and found to be clinically efficacious. Newer vaccine approaches such as using polysaccharide-protein conjugates and passive therapy with monoclonal or polyclonal immune sera offer some additional means to try and produce an effective immunotherapeutic reagent for this problematic pathogen.
Pier
Gerald B
GB
Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gpier@rics.bwh.harvard.edu
D000911:Antibodies, Monoclonal / Q000737:chemistry; D000942:Antigens, Bacterial / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002986:Clinical Trials as Topic; D000939:Epitopes; D006801:Humans; D007120:Immunochemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D014612:Vaccines
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000939:Epitopes; D008070:Lipopolysaccharides; D019081:O Antigens; D014612:Vaccines