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SipD and IpaD induce a cross-protection against Shigella and Salmonella infections.

ABSTRACT: Salmonella and Shigella species are food- and water-borne pathogens that are responsible for enteric infections in both humans and animals and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics require the development of broadly protective therapies. Those bacteria utilize a Type III Secretion System (T3SS), necessary for their pathogenicity. The structural proteins composing the T3SS are common to all virulent Salmonella and Shigella spp., particularly the needle-tip proteins SipD (Salmonella) and IpaD (Shigella). We investigated the immunogenicity and protective efficacy of SipD and IpaD administered by intranasal and intragastric routes, in a mouse model of Salmonella enterica serotype Typhimurium (S. Typhimurium) intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins. Mice immunized with SipD or IpaD were protected against lethal intestinal challenge with S. Typhimurium or Shigella flexneri (100 Lethal Dose 50%). We have shown that SipD and IpaD are able to induce a cross-protection in a murine model of infection by Salmonella and Shigella. We provide the first demonstration that Salmonella and Shigella T3SS SipD and IpaD are promising antigens for the development of a cross-protective Salmonella-Shigella vaccine. These results open the way to the development of cross-protective therapeutic molecules.

SUBMITTER: Jneid B

PROVIDER: S-EPMC7282677 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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SipD and IpaD induce a cross-protection against Shigella and Salmonella infections.

Jneid Bakhos B Rouaix Audrey A Féraudet-Tarisse Cécile C Simon Stéphanie S

PLoS neglected tropical diseases 20200528 5

Salmonella and Shigella species are food- and water-borne pathogens that are responsible for enteric infections in both humans and animals and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics require the development of broadly protective therapies. Those bacteria utilize a Type III Secretion System (T3SS), necessary for their pathogenicity. The s ...[more]

PMID: 32463817

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Project description:BackgroundSalmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine.Principal findingsWe investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant.Conclusions and significanceSalmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality.

Dataset Information

SipD and IpaD induce a cross-protection against Shigella and Salmonella infections.

Publications

SipD and IpaD induce a cross-protection against Shigella and Salmonella infections.

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