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Non-typhoidal salmonella vaccines

A Salmonella and vaccine technology, applied in the direction of antibacterial drugs, bacterial antigen components, depsipeptides, etc., can solve problems such as weakening of binding

Inactive Publication Date: 2011-10-05
THE UNIV OF BIRMINGHAM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, with OmpD - STm infection of porin-immunized mice abolishes protection and binding of antibodies from porin-immunized mice to bacterial cell wall preparations lacking OmpD is impaired

Method used

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  • Non-typhoidal salmonella vaccines
  • Non-typhoidal salmonella vaccines
  • Non-typhoidal salmonella vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Materials and methods

[0061] Mice, Bacterial Strains and Immunogens

[0062] Wild-type (WT) mice were obtained from domestic populations. The origin of genetically deficient mice has been reported elsewhere (Cunningham et al. (2007) J. Immunol. (Journal of Immunology) 178 , 6200-7 and Gaspal et al., (2008) J. Immunol. (Journal of Immunology) 180 , 2824-9), with the exception being the βδ TCR-deficient mouse, which was obtained from Jax. All mice and groups were age (6-12 weeks) and sex matched prior to use. Salmonella enterica typhimurium serotype SL1344 is a WT strain, and SL3261 is a well-described AroA-deficient attenuated strain. OmpD-deficient STm was generated on the SL3261 background.

[0063] Total Omp preparations were generated by extracting cell envelopes with 2% (v / v) Triton X-100 and harvesting by centrifugation as previously described. Purified porins were produced from ST (strain 9933) and STm (ATCC strain 14028) using well-established methods...

Embodiment 2

[0108] When appropriate, the following further work was carried out following the protocol in Example 1:

[0109] 1. In NTS, bacteremia often reflects disease severity. We therefore investigated the effect of porin immunization on bacteremia induced by subsequent infection with STm or STm lacking OmpR (resulting in defective OmpF and OmpC expression) or OmpD deficient STm. We show that porin immunization can eliminate bacteremia in STm infection ( Figure 5 , left panel) and can be seen after infection of porin-primed mice with OmpR-deficient STm ( Figure 5 , central panel), but rarely seen after infection with OmpD-deficient STm ( Figure 5 , right panel). This suggests that antibodies against porins, especially OmpD, can significantly reduce bacteremia.

[0110] 2. A single immunization with porins is sufficient to reduce the bacterial burden caused by STm. To assess whether two immunizations increased the beneficial effects of porin immunization, mice were immunized t...

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Abstract

OmpD of non-typhoidal Salmonella (NTS), e.g. as derivable from Salmonella Typhimurium, and immunogenic fragments thereof are proposed for use in treating or preventing NTS infection and / or disease. OmpD of S. paratyphi and fragments thereof are also now of interest for vaccine use.

Description

field of invention [0001] The present invention relates to vaccines for non-typhoidal salmonellae (NTS) infections and, in particular, provides such vaccines with immunogens that will generate antibodies targeting the outer membrane porin (OmpD). Preferably, for example, this may be OmpD itself, or a fragment of OmpD that retains the ability to induce effective antibodies against NTS, especially Salmoella enterica serotype Typhimurium - hereinafter referred to as STm. This polypeptide can be provided together with an adjuvant carrier molecule. It may be provided as part of a multi-subunit vaccine with one or more other antigens derived from Salmonella. Background of the invention [0002] Salmonella enterica typhi (Typhi) serotype (S.typhi), Salmonella paratyphi A (Salmonella paratyphiA) and non-typhoidal Salmonella (NTS) are the main pathogenic factors. Typhoid fever remains a global health problem, and in some areas such as sub-Saharan Africa, diseases caused by non-typh...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/255A61K39/02
CPCC07K14/255A61K2039/545A61K2039/521A61K39/00A61K39/0275A61P31/04A61P37/04Y02A50/30
Inventor 亚当·坎宁安
Owner THE UNIV OF BIRMINGHAM
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