PSEUDOMONAS-AERUGINOSA ANTIGENS AS POTENTIAL VACCINES

Pseudomonas aeruginosa is one of the most important opportunistic bact erial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeabil ity of the outer membrane and the presence of numerous multiple drug e fflux pumps. Various cell associated and secreted antigens of P. aerug inosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consis ting predominantly of alginate, was found to be heterogeneous in terms of size and immunogenicity. High molecular mass alginate components ( 30-300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10-30 kDa) possess conserved epitopes in ad dition to unique epitopes. Surface-exposed antigens including O-antige ns (O-specific polysaccharide of LPS) or H-antigens (flagellar antigen s) have been used for serotyping due to their highly immunogenic natur e. Chemical structures of repeating units of O-specific polysaccharide s have been elucidated and these data allowed the identification of 31 chemotypes of P, aeruginosa. Conserved epitopes among all serotypes o f P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce cross- protective immunity in mice against different P. aeruginosa immunotype s. To examine the protective properties of OM proteins, a vaccine cont aining P. aeruginosa OM proteins of molecular masses ranging from 20 t o 100 kDa has been used in pre-clinical and clinical trials. This vacc ine was efficacious in animal models against P. aeruginosa challenge a nd induced high levels of specific antibodies in human volunteers. Pla sma from human volunteers containing anti-P. aeruginosa antibodies pro vided passive protection and helped the recovery of 87% of patients wi th severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the effi cacy of ribosomal vaccines in humans is not yet known. A number of rec ent studies indicated the potential of some P. aeruginosa antigens tha t deserve attention as new vaccine candidates. The enter core of LPS w as implicated to be a ligand for binding of P. aeruginosa to airway an d ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inn er core are highly conserved and it has been demonstrated to be surfac e-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of resear chers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed p roteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly con served protein, WbpM, and P. aeruginosa with a deficiency in this prot ein produces only rough LPS and became serum sensitive. Results from t hese studies have provided the foundation for a variety of vaccine for mulations.