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-11141475-B2
Publication Date
2021-10-12
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 producing an immunogenic vaccine composition comprising an inactivated pathogen by contacting a pathogen having an RNA or DNA genome with a Fenton reagent. The Fenton reagent comprises hydrogen peroxide in combination with a transition metal selected from Cu and/or Fe, used in an amount and for a time-period sufficient to render the pathogen noninfectious while retaining pathogen immunogenicity.
The invention further describes substituted methisazone/isatin and related thiosemicarbazone chemical classes, including methisazone functional group/substructures and methisazone analogs. The disclosed methisazone-type reagent embodiments include methisazone, methisazone analogs, and agents having methisazone functional groups or substructures, and are directed to improving inactivation and immunogenicity kinetics while retaining antigenicity and immunogenicity.
In vaccine-production context, the disclosed approach uses dual oxidation in which hydrogen peroxide is combined with a transition metal in a Fenton-type oxidation, together with methisazone or methisazone analogs, to improve viral or bacterial inactivation rates while preserving antigenicity relative to hydrogen peroxide alone. Antigenicity and immunogenicity are discussed in relation to retaining neutralizing epitopes and hemagglutination activity, and to producing highly immunogenic inactivated vaccine compositions for eliciting immune responses in subjects.
Claims Coverage
The independent claim centers on contacting an RNA or DNA-genome pathogen with a Fenton reagent comprising hydrogen peroxide plus Cu and/or Fe for an amount and time sufficient to render the pathogen noninfectious while retaining immunogenicity. Dependent coverage adds pathogen scope, immunogenicity verification, and comparative performance relative to hydrogen peroxide alone.
Fenton reagent contacting to render noninfectious while retaining immunogenicity
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, in an amount and for a time-period sufficient to render the pathogen noninfectious while retaining pathogen immunogenicity.
Virus family scope
The pathogen is a virus belonging to Family Togaviridae, Flaviviridae, Poxviridae, or Orthomyxoviridae.
Immunogenicity verification using immunoassays and binding/agglutination assays
Verifying the immunogenicity of a noninfectious pathogen using pathogen-specific antibody, B cell, or T cell immunoassays, agglutination assays, or antigen-binding assays.
Comparative antigenicity and immunogenicity greater than hydrogen peroxide alone
The resulting antigenicity and/or immunogenicity is greater than that achieved by inactivating the pathogen with hydrogen peroxide alone.
The claims are directed to Fenton-type dual-oxidation inactivation using hydrogen peroxide with Cu and/or Fe, with retention of immunogenicity to produce an inactivated vaccine composition. The claim set also narrows the pathogen scope to specified virus families, adds immunogenicity verification using specified assays, and includes comparative performance greater than hydrogen peroxide alone.
Stated Advantages
Provides an inactivated pathogen that is noninfectious while retaining pathogen immunogenicity.
Produces an immunogenic vaccine composition with antigenicity and/or immunogenicity greater than inactivation with hydrogen peroxide alone.
Retains antigenicity and immunogenicity, including neutralizing epitopes and hemagglutination activity, while improving inactivation and immunogenicity kinetics when combined with methisazone-type reagents.
Improved viral and bacterial inactivation rates using dual oxidation with hydrogen peroxide and a transition metal in combination with methisazone or methisazone analogs.
Preserved antigenicity, including neutralizing epitopes and hemagglutination activity, relative to hydrogen peroxide alone.
Resulting immunogenicity and protection in vivo across multiple pathogens, as described in the partial content.
Documented Applications
Production of immunogenic inactivated vaccine compositions from RNA- or DNA-genome pathogens, including viruses and bacteria, for eliciting immune responses in subjects.
Inactivation of viruses described within Togaviridae, Flaviviridae, Poxviridae, and Orthomyxoviridae families, including examples CHIKV, DENV1-4, YFV, vaccinia virus, and influenza, to produce immunogenic vaccine compositions.
Inactivation of bacterial targets described as Campylobacter, including C. coli and C. jejuni, Listeria monocytogenes, and Shigella, to produce immunogenic vaccine compositions.
Vaccine antigen preparation and inactivation workflows for multiple pathogens including CHIKV, DENV, YFV, influenza, and Campylobacter.
In vivo immunogenicity and protection experiments across multiple pathogens as described in the partial content.
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