Pseudomonas aeruginosa antigens as potential vaccines

Abstract

Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting 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 addition to unique epitopes. Surface-exposed antigens including Oantigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce crossprotective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti-P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensit...

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

“…aeruginosa, a Gram-negative opportunistic pathogen, produces a number of virulence factors (63). One such factor is LPS, which is the major constituent (.90%) of the outer leaflet of the outer membrane of Gram-negative bacteria (64) and serves as the first protective layer for bacterial resistance to a variety of host defense molecules (50,63,65). The Abs described in this paper bind to the O-Ag, which is the major antigenic determinant of LPS (66).…”

Contribution of Burkholderia cenocepacia Flagella to Infectivity and Inflammation

“…Its protein nature, position on the surface of the bacteria, and simple isolation and purification may contribute to the success of a flagellin-based vaccine. Antibodies directed against flagella prevent motility and pathogenesis in mouse models (13,21,52). In a small vaccine trial, a bivalent P. aeruginosa flagellin vaccine that was administered intramuscularly to CF patients without P. aeruginosa showed promising results.…”

Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid

“…The host response to P. aeruginosa is a complex immune and inflammatory reaction that results in damage to the respiratory tract (1,2). Antibodies as well as cell-mediated immunity seem to be associated with protective immunity, but an efficient vaccine against pulmonary colonization with P. aeruginosa is not yet available (39)(40)(41)(42)(43)(44)(45)(46). Various components of P. aeruginosa have been tested as vaccine candidates in animal studies and humans, among them the outer membrane protein OprF.…”