DNA vaccine against crimean-congo hemorrhagic fever virus (CCHFV)
Inventors
Muthumani, Kar • Weiner, David
Assignees
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Publication Number
US-12296001-B2
Publication Date
2025-05-13
Expiration Date
Abstract
Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Crimean-Congo hemorrhagic fever virus (CCHFV) antigens. Immunomodulatory methods and methods of inducing an immune response against CCHFV are disclosed. CCHFV glycoprotein immunogens are disclosed.
Core Innovation
The invention relates to a DNA vaccine composition for Crimean-Congo hemorrhagic fever virus (CCHFV) that uses optimized synthetic consensus envelope glycoprotein (glycoprotein M) immunogens. The nucleic acid molecule encodes a consensus CCHFV antigen, where the antigen comprises an amino acid sequence selected from SEQ ID NO:2- or SEQ ID NO:4-derived sequences. The antigen sequences include fragments comprising 600 or more consecutive amino acids and variants linked to an IgE signal peptide.
The composition includes nucleic acid molecules formulated as plasmid and optionally RNA immunogens together with pharmaceutically acceptable excipients. Optional immune-modulating components are described as nucleic acid sequences encoding cytokines, including IL-12, IL-15, and IL-28. Delivery is described using in vivo electroporation to express the consensus envelope glycoprotein (glycoprotein M) immunogen.
The disclosed vaccine design is presented in connection with immunogenicity evaluation in mice, including humoral and cellular immune responses. Reported readouts include antibody binding and ELISA, immunofluorescence, and IFN-gamma ELISpot, with discussion of immunogenicity fold-increases. The disclosure also frames the constructs for therapeutic versus prophylactic use and includes vaccine design and optimization features such as codon and RNA optimization and Kozak sequence.
Claims Coverage
The independent claim covers a composition comprising a nucleic acid molecule encoding a consensus CCHFV antigen, with the antigen amino acid sequence selected from SEQ ID NO:2-derived sequences or SEQ ID NO:4-derived sequences. Dependent claims further specify sequence and nucleic-acid-form constraints, delivery by electroporation, optional co-encoded cytokines, and prophylactic immune-response induction concepts.
Consensus CCHFV antigen encoded by a nucleic acid sequence
A nucleic acid molecule comprising a nucleotide sequence that encodes a consensus Crimean-Congo hemorrhagic fever virus (CCHFV) antigen, wherein the antigen comprises the amino acid sequence selected from SEQ ID NO:2-derived sequences or SEQ ID NO:4-derived sequences.
600 or more consecutive amino acids with IgE signal peptide-linked variants
An antigen comprising a fragment of SEQ ID NO:2 that comprises 600 or more consecutive amino acids and optionally linked to an IgE signal peptide, and/or an antigen comprising a fragment of SEQ ID NO:4 that comprises 600 or more consecutive amino acids and optionally linked to an IgE signal peptide.
Expression plasmid nucleic acid molecule
The nucleic acid molecule is an expression plasmid.
Electroporation delivery to an individual
A composition from claim 1 formulated for delivering to an individual using electroporation.
Optional nucleic acid sequences encoding IL-12, IL-15, and IL-28
The composition further includes nucleic acid sequences encoding proteins selected from IL-12, IL-15 and IL-28.
Prophylactically effective immune response induction against CCHFV infection
A method for inducing an immune response to CCHFV infection by administering a prophylactically effective amount of the composition of claim 1 to an individual at an amount effective to generate an immune response against CCHFV.
Across the independent claim and its dependent refinements, coverage centers on a nucleic-acid-encoded consensus CCHFV envelope glycoprotein antigen using SEQ ID NO:2 and SEQ ID NO:4-derived amino acid sequences with 600 or more consecutive amino acids and optional IgE signal peptide linkage. Additional claim coverage limits the nucleic acid to an expression plasmid, narrows delivery to electroporation, optionally co-encodes IL-12, IL-15, and IL-28, and specifies prophylactic immune-response induction against CCHFV infection.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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