title: Rational design of Salmonella-based vaccination strategies.
abstract: A permanently growing body of information is becoming available about the quality of protective immune responses induced by mucosal immunization. Attenuated live bacterial vaccines can be administered orally and induce long-lasting protective immunity in humans without causing major side effects. An attenuated Salmonella enterica serovar Typhi strain is registered as live oral vaccine against typhoid fever and has been in use for more than two decades. Recombinant attenuated Salmonella strains are also an attractive means of delivering heterologous antigens to the immune system, thereby, stimulating strong mucosal and systemic immune responses and consequently provide an efficient platform technology to design novel vaccination strategies. This includes the choice of heterologous protective antigens and their expression under the control of appropriate promoters within the carrier strain. The availability of well-characterized attenuated mutants of Salmonella concomitantly supports fine tuning of immune response triggered against heterologous antigens. Exploring different mucosal sites as a potential route of immunization has to be taken into account as an additional important way to modulate immune responses according to clinical requirements. This article focuses on the rational design of strategies to modulate appropriate immunological effector functions on the basis of selection of (i) attenuating mutations of the Salmonella strains, (ii) specific expression systems for the heterologous antigens, and (iii) route of mucosal administration.
authors.affiliation: Berna Biotech Ltd., Bacterial Vaccine Research, Rehhagstr. 79, CH-3018 Berne, Switzerland. simone.spreng@bernabiotech.com
authors.forename: Simone
authors.initials: S
authors.lastname: Spreng
authors.forename: Guido
authors.initials: G
authors.lastname: Dietrich
authors.forename: Gerald
authors.initials: G
authors.lastname: Weidinger
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012475:Salmonella / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000209:etiology / Q000276:immunology; D019779:Salmonella enterica / Q000276:immunology / Q000472:pathogenicity; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology; D014169:Transformation, Bacterial; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000276:immunology*
chemical_list: D000941:Antigens; D001428:Bacterial Vaccines; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated