Immunotherapeutic potential of modified lipooligosaccharides/lipid A

Patent metadata

Field	Value
Publication number	US-10358667-B2
Application number	US-201414772282-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Mar 7, 2013
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

Embodiments of the disclosure provide for unique lipooligosaccharide/lipid A-based mimetics for use as adjuvants. Methods of generating lipooligosaccharide/lipid A-based mimetics are provided that utilize recombinantly engineered bacteria to produce the mimetics, including, for example, addition of one or more particular enzymes such as acyltransferases, deacylases, phosphatases, or glycosyltransferases.

First claim

What is claimed is:

1. A method of generating a lipooligosaccharide/lipid A-based mimetic composition, comprising the steps of:
obtaining a bacterial strain that expresses lipid A 1-phosphatase LpxE; and
producing the lipooligosaccharide/lipid A mimetic composition from the bacterial strain,
wherein the lipooligosaccharide/lipid A-based mimetic composition is modified to have one or more of the following modifications: removal of a 1-monophosphate group or having an additional sugar linked to the phosphate or ethanolamine thereof, and
wherein the bacterial strain is Yersinia pestis KIM6 pagP + ; Yersinia pestis ΔphoP-KIM6; or Yersinia pestis ΔphoP-pagP + KIM6.

2. The method of claim 1 , wherein the obtaining step is further defined as engineering the bacterial strain to have one or more of the modifications.

3. The method of claim 2 , wherein the engineering step comprises one or both of:
delivering a vector into the bacteria; or
bacterial conjugation.

4. The method of claim 2 , wherein the engineering step comprises delivering a vector into the bacteria, wherein the vector comprises sequence that encodes one or more nonendogenous lipid A biosynthesis enzymes.

5. The method of claim 1 , wherein the lipooligosaccharide/lipid A-based mimetic produced by the method has a modified number of phosphates compared to the endogenous bacterial lipid A molecule or a reference lipid A molecule.

6. The method of claim 1 , wherein the composition is a compound of the formula

wherein R 1 may be H, OH, protonated phosphate, a phosphate salt, a sugar phosphonate, or a mono-, di- or poly-saccharide,
wherein R 2 may be H, OH, a sugar phosphonate, or a mono-, di- or poly-saccharide,
R 3 may be OH or a mono-, di- or poly-saccharide,
R 4 , R 5 , R 6 and R 7 may be an alkyl or alkenyl chain of up to 13 carbons (for a chain of 16 carbons), and
R 8 , R 9 , R 10 and R 11 may be H, OH, or an alkyl or alkenyl ester of up to 16 carbons.

7. The method of claim 1 , wherein the composition is selected from the group consisting of

Assignees

• Univ Maryland
• Univ Washington Through Its Center For Commercialization

Inventors

• Ernst Robert K
• Pelletier Mark
• Hajjar Adeline

Classifications

• A61K39/0291

  Yersinia · CPC title

• A61K31/739

  Lipopolysaccharides · CPC title

• A61K2039/55572

  Lipopolysaccharides; Lipid A; Monophosphoryl lipid A · CPC title

• C12P19/26

  Preparation of nitrogen-containing carbohydrates · CPC title

• C12P19/44

  Preparation of O-glycosides, e.g. glucosides {(polysaccharides and not substituted disaccharides C12P19/04, C12P19/12)} · CPC title