Cross-protection provided by live Shigella mutants lacking major antigens

Valéria Szijártó, Éva Hunyadi-Gulyás, Levente Emody, Tibor Pál, Gábor Nagy

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalInternational Journal of Medical Microbiology
Volume303
Issue number4
DOIs
Publication statusPublished - May 2013

Keywords

  • Cross-protection
  • Immune response
  • Invasion plasmid
  • LPS
  • Live vaccine
  • Shigella

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases

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