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: Valéria Szijártó, Eva Hunyadi-Gulyás, Levente Emődy, Tibor Pál, Gábor Nagy
• Journal: International journal of medical microbiology : IJMM (Int J Med Microbiol) Vol. 303 Issue 4 Pg. 167-75 (May 2013) ISSN: 1618-0607 [Electronic] Germany
• PMID: 23567193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier GmbH. All rights reserved.

Chemical References

• Antigens, Bacterial
• Shigella Vaccines
• Vaccines, Attenuated

Topics

• Animals
• Antigens, Bacterial (genetics, immunology)
• Cross Protection
• Disease Models, Animal
• Dysentery, Bacillary (immunology, prevention & control)
• Female
• Gene Deletion
• Mice
• Mice, Inbred BALB C
• Mutation
• Shigella (genetics, immunology)
• Shigella Vaccines (administration & dosage, genetics, immunology)
• Vaccines, Attenuated (administration & dosage, genetics, immunology)