title: Cross-protection provided by live Shigella mutants lacking major antigens.
abstract: The immune response elicited by Shigella infections is dominated by serotype-specific antibodies recognizing the LPS O-antigens. Although a marked antibody response to invasion plasmid antigens (Ipa-s) shared by all virulent strains is also induced, the varying level of immunity elicited by natural infections is serotype-restricted. Previous vaccines have tried to mimic and achieve this serotype-specific, infection-induced immunity. As, however, the four Shigella species can express 50 different types of O-antigens, current approaches with the aim to induce a broad coverage use a mixture of the most common O-antigens combined in single vaccines. In the current study we present data on an alternative approach to generate immunity protective against multiple serotypes. Mutants lacking both major immune-determinant structures (i.e. the Ipa and O-antigens) were not only highly attenuated, but, unlike their avirulent counterparts still expressing these antigens, elicited a protective immune response to heterologous serotypes in a murine model. Evidence is provided that protection was mediated by the enhanced immunogenic potential of minor conserved antigens. Furthermore, the rough, non-invasive double mutants triggered an immune response different from that induced by the smooth, invasive strains regarding the isotype of antibodies generated. These non-invasive, rough mutants may represent promising candidates for further development into live vaccines for the prophylaxis of bacillary dysentery in areas with multiple endemic serotypes.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Pécs, Szigeti út 12, 7624 Pécs, Hungary.
authors.forename: Valéria
authors.initials: V
authors.lastname: Szijártó
authors.forename: Eva
authors.initials: E
authors.lastname: Hunyadi-Gulyás
authors.forename: Levente
authors.initials: L
authors.lastname: Emődy
authors.forename: Tibor
authors.initials: T
authors.lastname: Pál
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D017353:Gene Deletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012760:Shigella / Q000235:genetics / Q000276:immunology*; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated