Autodisplay

Abstract

Live attenuated Salmonella strains expressing antigens of pathogens are promising oral vaccine candidates. There is growing evidence that the topology of expression of the foreign antigens can have a dramatic impact on the immunogenicity. We examined the potential of the AIDA-I (Escherichia coli adhesin involved in diffuse adherence) autotransporter domain to display antigenic fragments of the urease A subunit of Helicobacter pylori for the induction of a protective immune response. In the murine H. pylori model, protection is mainly mediated by CD4؉ T cells, and we therefore used the AIDA-I expression system to successfully express both nearly full-length UreA and defined T-helper-cell epitopes on the surface of an attenuated Salmonella enterica serovar Typhimurium vaccine strain. Surface exposure of the large UreA fragment or of one UreA T-cell epitope mediated a significant reduction in the level of H. pylori in immunized mice after challenge infection, whereas conventional cytoplasmic expression of UreA in Salmonella had no effect. These results support the concept that surface display increases the immunogenicity of recombinant antigens expressed on oral live vaccine carriers and further demonstrate the feasibility of immunizing against H. pylori with Salmonella vaccine strains expressing CD4؉ T-cell epitopes.

Expression and Antigenic Evaluation of Helicobacter pylori UreB Fragment

“…These methods could be used to mathematically model the behavior of molecules in nature. Also, the data obtained by these methods could predict the natural reactions of molecules, such as binding antigens and antibodies (3,7).…”

“…These methods include homology modeling, docking, and 3D threading techniques, which are widely used along with ANN, SVM, and HMM to detect spatial epitopes. In the present study, we applied these techniques as major methods of identification (7,18). In general, methods used to identify antigenic epitopes should be structurally flexible on the protein surface, exposed to solvent, and contain charged amino acids and epitope hydrophilic amino acids (3,(18)(19)(20).…”

“…Helicobacter pylori produces a large amount of urease (10% -15% of the whole protein weight) (2,3,7), which is required for the survival and pathogenesis of H. pylori. Many enzymes reduce the acidity of the immediate environment of H. pylori by producing ammonia and carbonate from urea (4,6).…”

Adaptation of the Endogenous Salmonella enterica Serovar Typhi clyA -Encoded Hemolysin for Antigen Export Enhances the Immunogenicity of Anthrax Protective Antigen Domain 4 Expressed by the Attenuated Live-Vector Vaccine Strain CVD 908- htrA

“…Thus, ClyA itself could export antigen 1; antigen 2 could be surface exposed on vesicles via an independent surface expression system (such as the AIDA-I or MisL autotransporter fusions) (23,40,41); and antigen 3 could be targeted to the periplasmic space, where it could become entrapped within vesicles during ClyA release. Based on extensive experience with proteosome-based vaccines (i.e., antigen adsorbed to group B Neisseria meningitidis outer membrane protein vesicles), one would also expect the foreign antigens within the ClyA outer membrane vesicles to be more immunogenic than the same antigens delivered as soluble proteins (26).…”

Bacterial Surface Display of a Co-Factor Containing Enzyme, ω-Transaminase fromVibrio fluvialisUsing theBacillus subtilisSpore Display System

“…Beta-lactamase containing Zn 2þ , organophosphorous hydrolase containing Zn 2þ , and urease containing Ni 2þ were successfully surface displayed using appropriate hosts. 4,10,11) The functional adrenodoxin containing [2Fe-2S] cluster was chemically reconstituted after its display on the E. coli surface.…”