Cross-protection provided by live Shigella mutants lacking major antigens

• Published in: International journal of medical microbiology Vol. 303; no. 4; pp. 167 - 175
• Main Authors: Szijártó, Valéria, Hunyadi-Gulyás, Éva, Emődy, Levente, Pál, Tibor, Nagy, Gábor
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2013
• Subjects: Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Cross Protection; Disease Models, Animal; Dysentery, Bacillary - immunology; Dysentery, Bacillary - prevention & control; Female; Gene Deletion; Immune response; Infectious Disease; Invasion plasmid; Live vaccine; LPS; Medical Education; Mice; Mice, Inbred BALB C; Mutation; Shigella; Shigella - genetics; Shigella - immunology; Shigella Vaccines - administration & dosage; Shigella Vaccines - genetics; Shigella Vaccines - immunology; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Live vaccine; Cross-protection; Immune response; Invasion plasmid; Shigella; LPS
• ISSN: 1438-4221; 1618-0607
• DOI: 10.1016/j.ijmm.2013.02.017

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.