Vaccines comprising Mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy
Inventors
Reed, Steven G. • Duthie, Malcolm S.
Assignees
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Publication Number
US-11801290-B2
Publication Date
2023-10-31
Expiration Date
Abstract
Compositions and methods for preventing, treating and detecting leprosy are disclosed. The compositions generally comprise polypeptides comprising one or more Mycobacterium leprae antigens as well as polynucleotides encoding such polypeptides.
Core Innovation
The invention relates to leprosy prevention, treatment, and diagnosis using Mycobacterium leprae antigens formulated as fusion polypeptides. The fusion polypeptide comprises M. leprae antigens ML2028, ML2055, and ML2380, or M. leprae antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380. Fusion polypeptides and isolated polynucleotides encoding them are disclosed, including LEP-F1, ML89, and a specific fusion construct exemplified by SEQ ID NO:12 and related nucleic acids.
The disclosed embodiments further include immunostimulant-adjuvanted vaccine and composition formats in which the fusion polypeptide is combined with immunostimulants. Stated immunostimulant types include CpG-containing oligonucleotide, synthetic lipid A species including monophosphoryl lipid A (MPL, including 3D-MPL), saponins and saponin mimetics, amino alkyl glucosaminide 4-phosphates (AGPs), and Toll-like receptor (TLR) agonists, including GLA, imiquimod, gardiquimod, and resiquimod, with a GLA-SE context.
Diagnostic methods are disclosed for detecting antibodies binding the fusion polypeptide in biological samples. The document also describes immune stimulation and vaccination use cases, including combination with M. bovis BCG, and leprosy treatment including an option with chemotherapeutic agents. The disclosure further reports that recombinant ML2028/ML2055/ML2380 antigens formulated with GLA-SE reduce M. leprae burden and delay nerve damage in animal models.
Claims Coverage
The document provides two independent claims: one to a fusion polypeptide and one to a leprosy vaccine. Across the claim set, the inventive coverage is focused on defining the fusion polypeptide antigen set by specific M. leprae antigens and/or ≥90% amino acid sequence identity, and on specifying vaccine compositions by addition of enumerated immunostimulant selections, including named Toll-like receptor agonists and a GLA oil-in-water emulsion option.
Fusion polypeptide with ML2028/ML2055/ML2380 antigen set
A fusion polypeptide comprising Mycobacterium leprae antigens ML2028, ML2055, and ML2380, or M. leprae antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380.
Leprosy vaccine comprising ML2028/ML2055/ML2380 fusion polypeptide
A leprosy vaccine comprising a fusion polypeptide comprising Mycobacterium leprae antigens ML2028, ML2055, and ML2380.
Leprosy vaccine further including an immunostimulant
The leprosy vaccine is further formulated to include an immunostimulant as an additional vaccine component.
Immunostimulant selected from specified immunostimulant agents or combinations
The immunostimulant is chosen from specified immunostimulant agents or combinations thereof, including CpG-containing oligonucleotide, synthetic lipid A, monophosphoryl lipid A (MPL), saponins and saponin mimetics, amino alkyl glucosaminide 4-phosphates (AGPs), and Toll-like receptor agonists.
Immunostimulant selected from TLR4, TLR7/8, or TLR9 agonists
The immunostimulant is selected from TLR4, TLR7/8, or TLR9 agonists.
Immunostimulant selected from glucopyranosyl lipid A and named immunostimulant agents
The immunostimulant is selected from glucopyranosyl lipid A (GLA), CpG-containing oligonucleotide, imiquimod, gardiquimod, and resiquimod.
Overall, the claim coverage centers on a leprosy vaccine comprising a fusion polypeptide with ML2028, ML2055, and ML2380, with dependent claim refinements adding an immunostimulant component selected from defined sets, including Toll-like receptor agonists and named agents including GLA and imidazoquinolines.
Stated Advantages
Reduces M. leprae burden in animal models.
Delays nerve damage in animal models.
Retains fusion recognition and immune responses for a chimeric fusion protein.
Documented Applications
Leprosy prevention and/or treatment using immunostimulant-adjuvanted vaccine/composition embodiments based on the fusion polypeptide.
Leprosy diagnosis by detecting antibodies binding the fusion polypeptide in biological samples, including point-of-care assay formats such as lateral flow test strip and DPP assay.
Immune stimulation, including use in combination with M. bovis BCG.
Treatment of M. leprae infection, including an option of combining with chemotherapeutic agents.
Shortened chemotherapy time course is mentioned in the document context.
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