Cross-protection provided by live Shigella mutants lacking major antigens

Valéria Szijártó, E. Hunyadi-Gulyás, L. Emődy, Tibor Pál, Gábor Nagy

Research output: Contribution to journalArticle

5 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

Fingerprint

Cross Protection
Shigella
O Antigens
Antigens
Vaccines
Immunity
Infection
Bacillary Dysentery
Antibodies
Innate Immunity
Antibody Formation
Serogroup
Plasmids

Keywords

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

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Cross-protection provided by live Shigella mutants lacking major antigens. / Szijártó, Valéria; Hunyadi-Gulyás, E.; Emődy, L.; Pál, Tibor; Nagy, Gábor.

In: International Journal of Medical Microbiology, Vol. 303, No. 4, 05.2013, p. 167-175.

Research output: Contribution to journalArticle

@article{a2457ffc48154ddba7b63fb07aea5501,
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.",
keywords = "Cross-protection, Immune response, Invasion plasmid, Live vaccine, LPS, Shigella",
author = "Val{\'e}ria Szij{\'a}rt{\'o} and E. Hunyadi-Guly{\'a}s and L. Emődy and Tibor P{\'a}l and G{\'a}bor Nagy",
year = "2013",
month = "5",
doi = "10.1016/j.ijmm.2013.02.017",
language = "English",
volume = "303",
pages = "167--175",
journal = "International Journal of Medical Microbiology",
issn = "1438-4221",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "4",

}

TY - JOUR

T1 - Cross-protection provided by live Shigella mutants lacking major antigens

AU - Szijártó, Valéria

AU - Hunyadi-Gulyás, E.

AU - Emődy, L.

AU - Pál, Tibor

AU - Nagy, Gábor

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Cross-protection

KW - Immune response

KW - Invasion plasmid

KW - Live vaccine

KW - LPS

KW - Shigella

UR - http://www.scopus.com/inward/record.url?scp=84877106302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877106302&partnerID=8YFLogxK

U2 - 10.1016/j.ijmm.2013.02.017

DO - 10.1016/j.ijmm.2013.02.017

M3 - Article

C2 - 23567193

AN - SCOPUS:84877106302

VL - 303

SP - 167

EP - 175

JO - International Journal of Medical Microbiology

JF - International Journal of Medical Microbiology

SN - 1438-4221

IS - 4

ER -