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Conserved escherichia coli immunogens

A technology of Escherichia coli and immunogenic polypeptides, applied in the field of immunity, can solve problems such as not pointing out conservation

Inactive Publication Date: 2012-09-12
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this list does not indicate what is conserved among the major parts of pathogenic E. coli, what are the conserved regions among such conserved proteins, or which of the thousands of potential proteins could be used in vaccines or Generating an adequate immune response to protect against pathogenic E. coli requires screening a large number of proteins to identify the best candidates

Method used

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  • Conserved escherichia coli immunogens
  • Conserved escherichia coli immunogens
  • Conserved escherichia coli immunogens

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Embodiment Construction

[0417] each as described in more detail herein, bacterial Ig-like domain (group 1) protein (orf405), influenza antigen 43 (orf1364), NodT-family outer membrane factor lipoprotein efflux transporter (orf1767), gspK (orf3515) , gspJ (orf3516), tonB-dependent siderophore receptor (orf3597), pilin (orf3613), upec-948, upec-1232, A-chain precursor of type 1 pilin (upec-1875), yap The H homologue (upec-2820), hemolysin A (recp-3768) and Sel1 repeat-containing protein (upec-5211) have been expressed and purified and confer protection against ExPEC strains in an animal model of sepsis.

[0418] Sequences of orthologs were obtained from various other E. coli strains.

[0419] Each protein-orf353 (SEQ ID NO:1-amino acid 21-162), bacterial Ig-like domain (group 1) protein (orf405) (SEQ ID NO:9-amino acid 595-1008), influenza antigen 43 (orf1364 ) (SEQ ID NO:27-amino acids 53-629), NodT-family outer membrane factor lipoprotein efflux transporter (orf1767) (SEQ ID NO:41-amino acids 15-457...

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Abstract

Homologs of the E. coli proteins orf353, bacterial lg-like domain (group 1) protein (orf405), flu antigen 43 (orfl 364), NodT-family outer-membrane-factor-lipoprotein efflux transporter (orfl 767), gspK (orf3515), gspJ (orf3516), toriB-dependent siderophore receptor (orO597), fibrial protein (orf3613), upec-948, upec- 1232. A chain precursor of the type- 1 fimbria! protein (upec- 1875), yapH homolog (upec-2820), hemolysin A (recp-3768), and Sel l repeat-containing protein (upec-521 1 ) from several pathogenic strains of E. coli have been identified with regions within the proteins that are conserved across all E. coli. Fragments corresponding to the conserved regions, especially immunogenic fragments such a linear B-epitopes, are provided.; In addition, variants of the bacterial lg-l ike domain (group 1 ) protein (orf405), yapH homolog (upec2820) and two different fragments of hemolysin A (recp3768) are provided herein that have increased solubility as compared to the native protein where the variants still raise a substantially similar immune response in a subject as the corresponding native protein.

Description

technical field [0001] The present invention relates to immunization against pathogenic Escherichia coli strains. Background technique [0002] E. coli strains are generally classified as commensal or pathogenic, and pathogenic strains are subdivided as enteric or extraenteric. Pathogenic E. coli are discussed in more detail in reference 1 and are grouped into different pathotypes, a group of E. coli strains that use a common set of virulence factors to cause a common disease. Pathotyping of strains is a routine technique and can be performed by genotyping or phenotyping. A recent genotyping-based pathogenic typing method [2] employs DNA microarrays. [0003] Among enteric strains, at least six well-described pathotypes are known: enteropathogenic (EPEC), enterohemorrhagic (EHEC), enteroaggregative (EAEC), enteroinvasive (EIEC), enterotoxigenic (ETEC) and diffusion adhesion (DAEC). [0004] Extraintestinal pathogenic strains of E. coli (or 'ExPEC' strains [3, 4]) include...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/245A61K39/02
CPCA61K39/00A61K39/0258C07K14/245A61P31/04A61P37/04Y02A50/30
Inventor L·塞里诺M·R·丰塔纳D·G·莫里尔
Owner NOVARTIS AG
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