Nanoemulsion and methods of use thereof
Inventors
Khader, Shabaana Abdul • Ahmed, Mushtaq • Fattom, Ali • Smith, Douglas • Hamouda, Tarek
Assignees
Washington University in St Louis WUSTL • Bluewillow Biologics Inc
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Publication Number
US-11642405-B2
Publication Date
2023-05-09
Expiration Date
Abstract
The present disclosure relates to compositions and methods for inducing an immune response to a composition of the invention in a subject. Additionally, the present disclosure generally relates to methods for screening for immune response to a composition of the invention.
Core Innovation
A composition for intranasal administration is provided for treating or preventing a Mycobacterium infection in a subject in need thereof. The composition includes a nanoemulsion with droplets having an average diameter of less than about 1,000 nm and an aqueous phase, together with about 1% to about 80% (v/v) of at least one oil, about 0.001% to about 10% (v/v) of at least one surfactant, about 0.01% to about 50% (v/v) of at least one solvent, and less than about 5% (v/v) of at least one quaternary ammonium compound. The nanoemulsion is formulated for intranasal use alongside at least one isolated mycobacterial antigen, or an antigenic fragment thereof.
The composition is tied to a subcutaneously administered tuberculosis vaccine and specifies timing for intranasal administration of the nanoemulsion-plus-antigen composition. Administration of the composition is concurrent with or within 3 weeks after the subcutaneously administered tuberculosis vaccine. In the described context, the approach is intended to induce mucosal and systemic Th1/Th17 immune responses against tuberculosis, including IL-17 and IFN-b3.
The document further describes specific mycobacterial antigens and immune readouts in support of the approach. Examples include isolated Mycobacterium tuberculosis antigens such as ESAT-6 and Ag85B, as well as additional antigens listed in the content provided. Supporting example results describe that intranasal nanoemulsion plus Mtb antigens induce lung Th17 responses and improve protection while reducing lung inflammation and chemokines after Mycobacterium tuberculosis challenge versus controls, with immune responses compared using assays such as ELISpot and cytokine measurements.
Claims Coverage
The independent claim is directed to intranasal treatment or prevention of a Mycobacterium infection using a defined nanoemulsion composition combined with at least one isolated mycobacterial antigen, administered with a specified relationship to a subcutaneous tuberculosis vaccine. The coverage therefore hinges on three inventive elements: the specific nanoemulsion droplet/phase/component ranges, inclusion of isolated mycobacterial antigen (or fragment), and the concurrent/within-3-weeks timing relative to subcutaneous tuberculosis vaccination.
Intranasal nanoemulsion with sub-1,000 nm droplets and defined aqueous/oil/surfactant/solvent/quaternary ammonium ranges
Administering intranasally a composition comprising a nanoemulsion with droplets having an average diameter of less than about 1,000 nm, an aqueous phase, about 1% to about 80% (v/v) of at least one oil, about 0.001% to about 10% (v/v) of at least one surfactant, about 0.01% to about 50% (v/v) of at least one solvent, and less than about 5% (v/v) of at least one quaternary ammonium compound.
Isolated mycobacterial antigen included with the nanoemulsion
Including at least one isolated Mycobacterium tuberculosis antigen, or an antigenic fragment thereof, in the intranasally administered composition comprising the nanoemulsion.
Concurrent or within 3 weeks after subcutaneous tuberculosis vaccine administration
Wherein the subject has been subcutaneously administered a tuberculosis vaccine, and wherein administration of the intranasal composition is concurrent with or within 3 weeks after the subcutaneously administered tuberculosis vaccine.
Overall, the independent claim covers an intranasal nanoemulsion formulated with sub-1,000 nm droplets and specific aqueous/oil/surfactant/solvent/quaternary ammonium component ranges, combined with isolated mycobacterial antigen (or fragments), and given in a defined timing relationship (concurrent with or within 3 weeks after) a subcutaneous tuberculosis vaccine.
Stated Advantages
Inducing mucosal and systemic Th1/Th17 immune responses against tuberculosis.
Improving protection after Mycobacterium tuberculosis challenge versus controls.
Reducing lung inflammation and chemokines after Mycobacterium tuberculosis challenge versus controls.
Documented Applications
Treating or preventing a Mycobacterium infection in a subject by intranasal administration of a nanoemulsion composition comprising isolated mycobacterial antigens in timing relation to a subcutaneous tuberculosis vaccine.
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