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Combined enteropathogen recombinant construct

a technology of enteropathogens and recombinant constructs, which is applied in the field of recombinant constructs, can solve the problems of no fda-licensed vaccine for either pathogen, serious health threat to western travelers and young children, and etec is the most common cause of travelers' diarrhea. , to achieve the effect of reducing amino acid sequence length, avoiding undesirable associations, and reducing protease cleavag

Active Publication Date: 2017-09-21
UNIVERSITY OF GUELPH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]Campylobacter jejuni is associated with induction of Guillain-Barré Syndrome (GBS), a post-infectious polyneuropathy that can result in paralysis. The association is due to molecular mimicry between the sialic acid containing-outer core of the lipooligosaccharide (LOS) and human gangliosides (5, 6, 89, 91). Thus, antibodies generated against LOS cores result in an autoimmune response to human neural tissue. Use of capsule polysaccharide from C. jejuni can induce an immune response without the possible induction of Guillain-Barré Syndrome.
[0013]The embodied multipartite construct can contain a deletion of the N-terminal region of one or more fimbrial subunits to avoid undesirable associations with other monomers or multimers and to remove reduce amino acid sequence length between polypeptides to reduce the protease cleavage.

Problems solved by technology

Both pathogens are a serious health threat to western travelers and young children in resource-limited countries, making them apt target populations for a single or dual pathogen vaccine against ETEC and CJ.
No FDA-licensed vaccines are available for either pathogen.
Moreover, ETEC is the most common cause of travelers' diarrhea.
LT and STI intoxicate epithelial cells, resulting in fluid and electrolyte secretion and clinical diarrhea.
None has yet been shown to confer sufficiently high and broad levels of protection.
There are, however, significant challenges for ETEC vaccine development.
Also, the diversity of ETEC CFs poses issues for achievement of sufficiently broad coverage with inclusion of a realistic number of CFs.

Method used

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  • Combined enteropathogen recombinant construct
  • Combined enteropathogen recombinant construct
  • Combined enteropathogen recombinant construct

Examples

Experimental program
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Effect test

example 1

Conjugation of ETEC Polypeptides to C. jejuni Capsule Polysaccharide (CPS)

[0036]In a preferred embodiment, ETEC recombinant polypeptides or polypeptide constructs are conjugated to C. jejuni CPS. The CPS can be derived from a number of C. jejuni strains. In the embodiment, any CPS of any C. jejuni strain is envisioned to be conjugated to ETEC recombinant polypeptide constructs. Alternatively, Shigella LPS can be conjugated to ETEC recombinant polypeptide constructs.

[0037]The overall method of conjugating includes oxidizing C. jejuni CPS, for example, with NaIO4 in sodium acetate (pH 4.0). Oxidized CPSs were desalted with a 5 kDa cutoff membrane by stirred ultrafiltration, which is subsequently lypholized. ETEC proteins are then added. The stoichiometery protein to CPS can vary, however, a typical ratio is 1:2 protein to CPS by mass. The concentration of components can be by any method. However, for example, polysaccharide concentration was determined by antrhone assay and protein co...

example 2

Anti-Class 5 ETEC, CS3 or CS6 Constructs

[0047]Anti-ETEC constructs that are contemplated to be conjugated to C. jejuni polysaccharide comprise the structures as illustrated in FIG. 1 and FIG. 2. FIG. 1 illustrates the basic recombinant construct design. As diagrammed in FIG. 1 the construct design comprises one, or more ETEC major or minor fimbrial subunits or fragments of major fimbrial subunits, containing the donor strand, derived from the same ETEC fimbrial type, which are connected, via polypeptide linkers and stabilized by donor strand complementation. The construct can contain a deletion of the N-terminal region of the N-terminal subunit. This feature prevents undesirable associations with other monomers or multimers. The C-terminal subunit is connected to and stabilized by a donor β strand, connected to the subunit via a polypeptide linker, wherein the donor β strand is either derived from the adjacent subunit (i.e., homologous) or from a different subunit of the same fimbri...

example 3

C. jejuni Capsule Polysaccharides

[0099]Recent development of a molecular CPS typing system re-enforced the strong correlation between CPS and Penner types (Poly, et al., J. Clin. Microbiol. 49: 1750 (2011)). Both Penner serotyping and molecular CPS typing have revealed the predominance of a handful of CPS types worldwide. Also, despite over 60 Penner serotypes having been identified, most Campylobacter diarrheal disease is caused by C. jejuni expressing only a limited number of serotypes. Therefore, only selected strains of C. jejuni, predicated on epidemiological studies, provides suitable candidate strains for development of vaccine compositions. However, despite the importance of this organism to human disease, there are no licensed vaccines against C. jejuni.

[0100]C. jejuni capsule polysaccharide (CPS) was extracted from C. jejuni strains selected based on their association with diarrheal disease. CPS from bacteria was extracted by hot water-phenol extraction for 2 h at 70° C. ...

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Abstract

The inventive subject matter relates to a construct comprising antigens derived from multiple enterobacteria including Campylobacter jejuni capsule polysaccharide polymer, enterotoxigenic Escherichia coli recombinant polypeptide construct and lipopolysaccharide from Shigella spp. The subject invention also relates to a method of inducing an immune response utilizing the inventive composition.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application is a Continuation-in-Part to U.S. Nonprovisional application Ser. No. 11 / 340,003, filed Jan. 10, 2006, which claims priority to U.S. Provisional application 60 / 642,771 filed Jan. 11, 2005, and a Continuation-in-Part to U.S. Nonprovisional application Ser. No. 11 / 524,057 filed Sep. 20, 2006, which claims priority to U.S. Provisional application 60 / 722,086, filed Sep. 21, 2005, and a Continuation-in-Part to U.S. Nonprovisional application Ser. No. 14 / 048,264, filed Oct. 8, 2013, which claims priority to U.S. Provisional application 61 / 727,943, filed Nov. 19, 2012, the contents of which are herein incorporated by reference. This application also claims priority to U.S. Provisional application 62 / 054,454, filed 24 Sep. 2014, U.S. Provisional application 62 / 127,927, filed Mar. 4, 2015, U.S. Provisional application 62 / 165,301, filed May 22, 2015, U.S. Provisional application 62 / 127,935, filed Mar. 4, 2015, and U.S. Provisional...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/48C07K14/245
CPCA61K47/646A61K39/00A61K47/6415C07K14/245C07K16/1232C07K2317/55C07K2319/35A61K39/0283A61K39/105C07K16/1267C07K16/44C07K2317/76A61K39/0258A61K2039/55505A61K2039/70A61K2039/6037Y02A50/30
Inventor GUERRY, PATRICIAMONTEIRO, MARIO ARTURSAVARINO, STEPHEN
Owner UNIVERSITY OF GUELPH
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