Marburgvirus consensus antigens, nucleic acid constructs and vaccines made therefrom, and methods of using same

Inventors

Weiner, David • Patel, Ami • ELLIOTT, Sarah

Assignees

University of Pennsylvania Penn • Wistar Institute of Anatomy and Biology

Abstract

Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Marburgvirus filovirus glycoprotein immunogens. Immunomodulatory methods and methods of inducing an immune response against Marburgvirus are disclosed. Method of preventing infection by Marburgvirus and methods of treating individuals infected with Marburgvirus are disclosed. Consensus Marburgvirus filovirus glycoprotein immunogens are disclosed.

Core Innovation

The invention relates to an immunogenic composition comprising a nucleic acid molecule encoding a peptide selected from specific amino acid sequences and immunogenic fragments derived from SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6, with defined percent identity and coverage thresholds. The composition includes both entire amino acid sequences and fragment variants, where the fragment variants are defined by at least about 90% identity over at least 60% of a reference amino acid sequence or by at least 70% of the amino acid sequence length criteria.

The nucleic acid molecule is optionally operably linked to regulatory elements that include start codon, stop codon, and an IgE leader sequence, and can be provided in the context of an expression vector. Additional composition options include pharmaceutically acceptable excipients and/or adjuvants, including cytokine genes, with immune-response related objectives expressed for humoral IgG and neutralizing antibodies and for cellular CD8+ and CD4+ T-cell responses.

The document also describes administering the nucleic acid immunogenic composition in prophylactic and therapeutic settings against Marburgvirus infection and Marburgvirus hemorrhagic fever. DNA delivery is described as occurring via in vivo electroporation, including constant current/feedback electroporation device approaches, and immunogenicity outcomes are described using multiple lineage-derived consensus GP constructs showing expression, antibody binding, and IFN-b3 ELISPOT T-cell responses after vaccination and broadened responses after boosting or combining constructs.

Claims Coverage

The provided claims include four independent claim sets centered on nucleic acid-encoded Marburgvirus consensus envelope glycoprotein (GP) immunogens with defined percent-identity and fragment-coverage criteria, plus an optional operably linked IgE leader regulatory context. The core inventive features are the specific selection of amino-acid/fragment sequences and the identity/coverage thresholds.

The claims are primarily directed to nucleic acid molecules and peptides encoding or defined by Marburgvirus consensus GP-derived amino acid sequences and immunogenic fragments selected from SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6, with percent identity and fragment-coverage criteria. The nucleic-acid claim set coverage additionally supports operably linking to regulatory sequences including an IgE leader sequence and an expression-vector context.

Stated Advantages

Documented Applications

No documented applications found