Inactivating pathogens and producing highly immunogenic inactivated vaccines using a dual oxidation process
Inventors
Amanna, Ian J. • Poore, Elizabeth A.
Assignees
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Publication Number
US-12102676-B2
Publication Date
2024-10-01
Expiration Date
Abstract
Provided are surprisingly effective methods for inactivating pathogens, and for producing highly immunogenic vaccine compositions containing an inactivated pathogen rendered noninfectious by exposure to a Fenton reagent, or by exposure to a Fenton reagent or a component thereof in combination with a methisazone reagent selected from the group consisting of methisazone, methisazone analogs, functional group(s)/substructure(s) of methisazone, and combinations thereof. The methods efficiently inactivate pathogens, while substantially retaining pathogen antigenicity and/or immunogenicity, and are suitable for inactivating pathogens, or for the preparation of vaccines for a wide variety of pathogens with genomes comprising RNA or DNA, including viruses and bacteria. Also provided are highly immunogenic inactivated vaccine compositions prepared by using any of the disclosed methods, and methods for eliciting an immune response in a subject by administering such vaccine compositions.
Core Innovation
The invention relates to a method for producing an immunogenic vaccine composition comprising an inactivated pathogen. The method contacts a pathogen having an RNA or DNA genome with a Fenton reagent comprising hydrogen peroxide in combination with a transition metal selected from Cu and/or Fe, together with one or more compounds of formula I, II, III, IV, or V.
The contact is performed in an amount and for a time-period sufficient to render the pathogen noninfectious while retaining pathogen immunogenicity. The resulting inactivated pathogen retains antigenicity and/or immunogenicity, and the compounds include pharmaceutically acceptable salts and embodiments defined by variables R1, R2, R3, and X across formulas I through V.
The document also addresses verification of immunogenicity using pathogen-specific antibody, B cell and/or T cell immunoassays, agglutination assays, or antigen-binding assays. The platform is presented as applicable to multiple viral and bacterial species, and to vaccine compositions such as lyophilized and purified inactivated immunogenic vaccine compositions.
Claims Coverage
The independent claims include one method claim covering a Fenton-type inactivation approach using hydrogen peroxide, a Cu and/or Fe transition metal, and one or more specified formula I–V compounds, for rendering RNA or DNA pathogens noninfectious while retaining immunogenicity. Dependent claim refinements narrow pathogen scope, specify immunogenicity verification modalities, and introduce comparative antigenicity/immunogenicity performance versus hydrogen peroxide alone, with further narrowing to specific formula-variable embodiments.
Fenton reagent with transition metal and hydrogen peroxide plus formula I–V compounds for pathogen inactivation
Contacting a pathogen having an RNA or DNA genome with a Fenton reagent comprising hydrogen peroxide in combination with a transition metal selected from Cu and/or Fe and one or more compound(s) of formula I, II, III, IV, or V, for an amount and time-period sufficient to render the pathogen noninfectious while retaining pathogen immunogenicity, wherein the compounds are defined by variables for each formula set and include pharmaceutically acceptable salts.
Comparative retained antigenicity and immunogenicity versus hydrogen peroxide alone
The immunogenic vaccine composition has an antigenicity and/or immunogenicity greater than that obtainable by inactivation of the pathogen using hydrogen peroxide alone.
Virus or bacterium pathogen scope
The method is performed using a pathogen that is either a virus or a bacterium.
Immunogenicity verification using specified immunoassays and binding or agglutination assays
Verifying the immunogenicity of the noninfectious pathogen using pathogen-specific antibody, B cell or T cell immunoassays, agglutination assays, or antigen-binding assays.
Formula I–V compound embodiment narrowing for specified substituent identities
Further limiting the method by specifying substituent identities for variables X and R1 in formula II, X, R1, and R2 in formula III, and R2 and R3 in formulas IV and V, with corresponding named examples.
Overall, the claim coverage centers on producing an immunogenic vaccine composition by contacting RNA or DNA pathogens with a Fenton reagent comprising hydrogen peroxide plus Cu and/or Fe together with specified formula I–V compounds, to inactivate the pathogen without losing immunogenicity, with dependent refinements for comparative performance, pathogen scope, immunogenicity verification, and narrowed formula-variable embodiments.
Stated Advantages
Improved antigenicity and/or immunogenicity compared to inactivation using hydrogen peroxide alone.
Render pathogens noninfectious while retaining pathogen immunogenicity.
Documented Applications
Production of inactivated immunogenic vaccine compositions for multiple viral and bacterial pathogens, including CHIKV, DENV1-4, YFV, vaccinia virus, influenza A, Campylobacter, Listeria monocytogenes, and Shigella dysenteriae.
Vaccine composition formats and use, including lyophilized and purified inactivated immunogenic vaccine compositions, optionally adjuvanted and optionally preservative-free.
Assessment or verification of retained immunogenicity using pathogen-specific antibody, B cell or T cell immunoassays, agglutination assays, or antigen-binding assays.
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