Filovirus consensus antigens, nucleic acid constructs and vaccines made therefrom, and methods of using same
Inventors
Weiner, David B. • Patel, Ami • Yan, Jian
Assignees
University of Pennsylvania Penn • Wistar Institute of Anatomy and Biology • Inovio Pharmaceuticals Inc
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Publication Number
US-12240872-B2
Publication Date
2025-03-04
Expiration Date
Abstract
Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Ebolavirus glycoproteinimmunogens are disclosed. The coding sequences optionally include operable linked coding sequence that encode a signal peptide. Immunomodulatory methods and methods of inducing an immune response against Ebolavirus are disclosed. Method of preventing Ebolavirus and methods of treating individuals infected with Ebolavirus are disclosed. Consensus Ebolavirus proteins are disclosed.
Core Innovation
The invention relates to filovirus consensus envelope glycoprotein immunogens, in particular an isolated nucleic acid molecule encoding a consensus Zaire ebolavirus envelope glycoprotein immunogen (ZEBOVCON2). ZEBOVCON2 comprises an amino acid sequence as set forth in SEQ ID NO:68 or a fragment comprising at least 600 consecutive amino acid residues of SEQ ID NO:68.
The nucleic-acid vaccine compositions include nucleic acids encoding ZEBOVCON2 and may include linkage components such as an IgE signal peptide or an IgG signal peptide. The disclosed nucleic acid constructs are formulated for delivery using plasmids and in vivo electroporation, and the partial content describes a polyvalent filovirus DNA vaccine design using ZEBOV/SUDV GP consensus strategies and a three-plasmid strategy including pEBOZ, pEBOS, and pMARV.
The compositions can further include nucleic acid sequences encoding cytokines or immunomodulators such as IL-12, IL-15, and IL-28. The partial content reports functional characterization by ELISA binding and viral neutralization assays, IFNγ ELISPOT, and FACS phenotyping, and describes prophylactically effective and therapeutically effective use against Marburgvirus and Ebolavirus.
Claims Coverage
The claim coverage centers on an isolated nucleic acid molecule encoding the consensus Zaire ebolavirus envelope glycoprotein immunogen ZEBOVCON2 defined by SEQ ID NO:68 or a minimum-length fragment. The coverage further includes fragment-length constraints, optional signal peptide linkage, electroporation-based delivery to an individual, and inclusion of nucleic acid sequences encoding IL-12, IL-15, and IL-28.
Isolated nucleic acid encoding ZEBOVCON2 defined by SEQ ID NO:68 or a minimum fragment
An isolated nucleic acid molecule comprising a nucleic acid encoding a consensus Zaire ebolavirus envelope glycoprotein immunogen (ZEBOVCON2), wherein the ZEBOVCON2 comprises an amino acid sequence as set forth in SEQ ID NO:68, or a fragment of an amino acid sequence comprising at least 600 consecutive amino acid residues of SEQ ID NO:68.
Minimum fragment length with alternative consecutive-residue thresholds
The claimed nucleic acid comprises a fragment of an amino acid sequence comprising at least 600 consecutive amino acid residues of SEQ ID NO:68, wherein the fragment comprises at least 630 consecutive amino acids or at least 660 consecutive amino acids of SEQ ID NO:68.
ZEBOVCON2 linked to an IgE signal peptide
The isolated nucleic acid molecule is defined in that ZEBOVCON2 is linked to an IgE signal peptide.
Electroporation delivery to an individual
A composition is formulated for delivery to an individual using electroporation.
Composition including nucleic acid sequences encoding IL-12, IL-15, and IL-28
The claimed composition additionally includes nucleic acid sequences encoding proteins selected from IL-12, IL-15, and IL-28.
Overall, the claim set covers isolated nucleic acids encoding ZEBOVCON2 defined by SEQ ID NO:68 or minimum-length fragments, with optional IgE signal peptide linkage, electroporation delivery to an individual, and co-encoding of IL-12, IL-15, and IL-28.
Stated Advantages
Complete protection of guinea pigs against gpMARV and gpZEBOV challenge after two doses.
Complete single-dose protection of mice against mouse-adapted ZEBOV.
Robust binding/neutralizing antibodies and broad, polyfunctional T-cell responses with identified immunodominant and subdominant epitopes.
Documented Applications
DNA immunization in rodents.
Preclinical challenge studies in guinea pigs and mice.
Expression confirmation in HEK293T cells by Western immunoblot and FACS.
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