Immunogenic trehalose compounds and uses thereof
Inventors
Burkhart, David • Evans, Jay • Johnson, Craig • Ryter, Kendal T. • Smith, Alyson • Abdelwahab, Walid Abdelwahab Marzouky
Assignees
University of Montana Missoula
Publication Number
US-11572381-B2
Publication Date
2023-02-07
Expiration Date
2039-03-01
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Abstract
Disclosed herein are immunogenic trehalose compounds and methods of use thereof, for example as vaccine adjuvants.
Core Innovation
The invention discloses immunogenic trehalose compounds of formula (I) and methods of their use, particularly as vaccine adjuvants. The compounds are designed with specific chemical groups, such as azido, alkynyl, or five-membered heteroaryl rings at defined positions, and can be tailored as symmetrical or asymmetrical molecules to optimize immune-modulating properties and formulation characteristics.
The background addresses the ongoing need for adjuvants that induce Th17 or Th17/Th1-type immune responses, which are crucial for effective vaccines against diseases caused by certain bacterial and fungal pathogens, as well as cancer and autoimmune diseases. Existing adjuvants mainly favor Th2 or Th1 responses and only one known Th17-promoting adjuvant has reached early clinical trials, highlighting the gap this invention aims to fill.
The trehalose-based compounds described can act as Th17 or Th17/Th1-inducing adjuvants, enhancing immune responses when used alone or in combination with antigens. The compounds have been shown to stimulate cytokine production such as IL-6 and TNFα in human and murine immune cells, and may exhibit improved physicochemical and immunological properties, particularly when synthesized as asymmetric molecules. These compounds are therefore asserted to provide a new class of adjuvants for advancing vaccine and therapeutic development in infectious diseases, cancer, and autoimmune conditions.
Claims Coverage
The patent contains multiple independent claims that define inventive features for immunogenic trehalose compounds, compositions, and related methods.
Trehalose compound of formula (I) with specific substituents
A compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: - R1 is selected from azido, alkynyl, or a five-membered heteroaryl ring containing 1-3 heteroatoms (N, O, S), optionally substituted with R3 - R2 is selected from azido, alkynyl, or a five-membered heteroaryl ring containing 1-3 heteroatoms (N, O, S), optionally substituted with R4 - At least one of R1 and R2 is heteroaryl - R3 and R4 are each independently selected from Ar, alkyl, heteroalkyl, alkenyl, and heteroalkenyl - Ar is an aryl or heteroaryl, optionally substituted with hydroxy, alkoxy, alkyl, or heteroalkyl - Each alkyl or heteroalkyl may be unsubstituted or substituted with hydroxy, amino, oxo, thioxo, halo, or haloalkyl
Immunomodulatory composition comprising the inventive trehalose compound
An immunomodulatory composition containing an effective amount of a compound of formula (I) as described above, or a pharmaceutically acceptable salt thereof.
Adjuvant composition comprising the inventive trehalose compound
An adjuvant composition comprising an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof.
Vaccine composition containing antigen and the inventive compound as adjuvant
A vaccine composition comprising: - An antigen - An adjuvant composition including an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof
Method for inducing an enhanced immune response
A method of inducing an enhanced immune response in a subject, comprising administering to the subject an immunogenic or adjuvant composition containing the compound of formula (I) or its pharmaceutically acceptable salt.
Method for inducing or enhancing immunogenicity of an antigen
A method for inducing or enhancing immunogenicity of an antigen in a subject, comprising administering a vaccine composition including the antigen and an adjuvant composition with an effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
Method of modulating immune response in a subject
A method of modulating an immune response in a subject, comprising administering to the subject the immunomodulatory composition described, which may be administered as a monotherapy.
Method for treatment in subjects suffering from cancer, autoimmune disorders, or infectious diseases
A method as described above, wherein the subject is suffering from cancer, an autoimmune disorder, or an infectious disease.
The claims comprehensively cover the composition and structure of novel trehalose-based compounds, their use as vaccine adjuvants or immunomodulators, and methods for enhancing immune responses or treating diseases by administering these agents.
Stated Advantages
The compounds can induce Th17 or Th17/Th1-type immune responses, which are important for effective vaccination against certain bacterial and fungal pathogens, as well as for cancer and autoimmune diseases.
Asymmetric molecules exhibit enhanced physiochemical properties such as lower hydrophobicity, better solubility, and optimized packing parameters for improved formulation, pharmacokinetics, and immune modulation compared to symmetric molecules.
The compounds may form cubosomal or liquid crystal structures that confer improved bioavailability and formulation stability.
Some compounds show higher cytokine induction and better aqueous formulatability, potentially allowing for more pharmaceutically acceptable delivery.
Documented Applications
Use as vaccine adjuvants to stimulate Th17 or Th17/Th1 immune responses against bacterial and fungal pathogens, such as Mycobacterium tuberculosis, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Candida albicans, and Aspergillus fumigatus.
Use in the treatment or prevention of cancer by inhibiting or reducing the growth or proliferation of cancer cells.
Use in the treatment and prevention of autoimmune disorders.
Use as immunomodulatory agents for enhancing or modulating immune responses, either as a monotherapy or in combination with antigens.
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