Vaccines against Nipah virus, and methods of using same
Inventors
Muthumani, Kar • Weiner, David
Assignees
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Publication Number
US-12357683-B2
Publication Date
2025-07-15
Expiration Date
Abstract
An aspect of the present invention is related to nucleic acid constructs capable of expressing at least one Nipah virus (NiV) antigen that elicits an immune response in a mammal against NiV virus, and methods of use thereof.
Core Innovation
The invention relates to nucleic-acid vaccine compositions encoding at least one consensus Nipah virus (NiV) antigen, where the nucleic acid molecule comprises a sequence selected from the group consisting of a nucleotide sequence having at least 98% identity over an entire length of SEQ ID NO:1 and SEQ ID NO:5, an immunogenic fragment comprising at least 98% identity over at least 60% of the nucleotide sequence selected from SEQ ID NO:1 and SEQ ID NO:5, and the nucleotide sequence selected from SEQ ID NO:1 and SEQ ID NO:5. The consensus NiV antigens include optimized consensus NiV antigen sequences, including NiV fusion (F) and glycoprotein (G) antigens.
The described nucleic acids include operable-linkage variants such as IgE leader-fused constructs, with operably linked regulatory sequences comprising start codon and stop codon arrangements. The constructs also include defined consensus nucleotide and amino-acid sequences, including specified SEQ ID NO combinations for the F and G antigen sequences, and additional construct linkage features such as an operably linked nucleotide sequence including SEQ ID NO:9.
The document further describes delivery and immunogenic-use concepts for inducing immune responses using nucleic acids, including expression vectors, plasmids, and viral particles, and administration concepts involving electroporation and injection. Immunogenicity outcomes in mice are described, including IFN-gamma ELISpot T-cell responses and antigen-specific IgG binding, supporting prophylactic and/or therapeutic induction against NiV infection and encephalitis.
Claims Coverage
The independent claim covers a nucleic acid molecule encoding at least one consensus NiV antigen, with inventive features based on specific SEQ ID NO:1 and SEQ ID NO:5 sequence-identity criteria and/or inclusion of an immunogenic fragment. Dependent claim refinements add nucleic acid type, operably linked regulatory elements including an IgE leader, linkage to an additional named sequence, and delivery or disease embodiment constraints for methods.
Encoding consensus Nipah virus antigen with defined sequence identity or immunogenic fragment
A nucleic acid molecule encoding at least one consensus Nipah virus (NiV) antigen, wherein the nucleic acid molecule comprises a sequence selected from the group consisting of a nucleotide sequence having at least 98% identity over an entire length of the nucleotide sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:5, an immunogenic fragment comprising at least 98% identity over at least 60% of the nucleotide sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:5, and the nucleotide sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:5.
Nucleic acid molecule selected as DNA or RNA
The nucleic acid molecule is selected from DNA molecules and RNA molecules.
Operably linked regulatory sequences including an IgE leader
The nucleic acid molecule includes operably linked regulatory sequences comprising a start codon, an IgE leader sequence coding nucleotide sequence, and a stop codon.
Operable linkage to an additional nucleotide sequence
A nucleic acid molecule is operably linked to a nucleotide sequence encoding SEQ ID NO:9.
Administration by electroporation and/or injection
Administration is performed using at least one of electroporation or injection.
Targeting NiV-associated pathology as NiV infection and/or encephalitis
The NiV-associated pathology is at least one of NiV infection or encephalitis.
The coverage centers on nucleic acids encoding consensus NiV antigens defined by specific identity thresholds to SEQ ID NO:1 and SEQ ID NO:5 and/or immunogenic fragments, with construct features including DNA/RNA selection, operably linked regulatory sequences with an IgE leader, and operable linkage to SEQ ID NO:9. Method coverage is further constrained by administration via electroporation and/or injection and by NiV-associated pathology embodiments of NiV infection and/or encephalitis.
Stated Advantages
Supports prophylactic and/or therapeutic induction against NiV infection and encephalitis, supported by described immunogenicity outcomes including IFN-gamma ELISpot T-cell responses and antigen-specific IgG binding.
Documented Applications
Prophylactic and/or therapeutic induction against NiV infection and encephalitis, as supported by described mouse immunogenicity outcomes including IFN-gamma ELISpot T-cell responses and antigen-specific IgG binding.
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