Vector-based attenuated poxvirus vaccines

Inventors

Howley, Paul

Assignees

SEMENTIS Ltd

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Publication Number

US-10905759-B2

Patent

Publication Date

2021-02-02

Expiration Date


Abstract

The present invention relates to a composition for raising an immune response in animal which decreases the risk of chikungunya and smallpox infection, Zika virus and smallpox infection, and/or chikungunya, Zika virus and smallpox infection. The composition comprises a pharmaceutically acceptable carrier and an attenuated poxvirus, wherein the poxvirus genome comprises a nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and/or the PrME of Zika virus.

Core Innovation

The invention provides an immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus. The attenuated poxvirus genome comprises nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and nucleic acid sequence encoding the PrME polyprotein of Zika virus, and further comprises deletion of at least one gene which encodes an endogenous essential assembly or maturation protein and/or increases immunogenicity of the composition.

The invention further provides an immunogenic composition that uses an attenuated poxvirus genome comprising a nucleic acid sequence encoding the PrME polyprotein of Zika virus. The attenuated poxvirus further comprises deletion of at least one gene which encodes an endogenous essential assembly or maturation protein and/or increases immunogenicity of the composition. The described intent is to raise protective immune responses against chikungunya, Zika, and/or smallpox.

The attenuation is achieved by deleting endogenous essential assembly or maturation genes within the poxvirus genome. The partial content additionally identifies illustrative gene targets for attenuation, including D13L and B7R-B8R. The described poxvirus vectors include modified vaccinia Ankara (MVA) and vaccinia-based strains such as vaccinia/CVA and vaccinia Copenhagen (COP), with the overall approach based on heterologous antigen expression in an attenuated poxvirus vector.

Claims Coverage

The provided claims include two independent claims. Across these, the independent claim set covers an immunogenic composition with a pharmaceutically acceptable carrier, an attenuated poxvirus, specific nucleic acid encoding heterologous polyproteins (chikungunya 26S subgenomic polyprotein and/or Zika PrME polyprotein), and deletion of at least one endogenous essential assembly/maturation gene and/or a gene that increases immunogenicity, with dependent claim refinements specifying example poxvirus types, carrier adjuvants, and specific deletion targets or administration aims.

Immunogenic composition with chikungunya 26S and Zika PrME encoding attenuated poxvirus plus essential assembly/maturation deletion

An immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus, wherein the attenuated poxvirus genome comprises a nucleic acid sequence encoding the 26S subgenomic polyprotein of chikungunya virus and a nucleic acid sequence encoding the PrME polyprotein of Zika virus and further comprises deletion of at least one gene which encodes an endogenous essential assembly or maturation protein and/or increases immunogenicity of the composition.

Immunogenic composition with Zika PrME encoding attenuated poxvirus plus essential assembly/maturation deletion

An immunogenic composition comprising a pharmaceutically acceptable carrier and an attenuated poxvirus, wherein the attenuated poxvirus genome comprises a nucleic acid sequence encoding the PrME polyprotein of Zika virus and further comprises deletion of at least one gene which encodes an endogenous essential assembly or maturation protein and/or increases immunogenicity of the composition.

Attenuated poxvirus selected from specified poxvirus types

The immunogenic composition uses an attenuated poxvirus selected from vaccinia, cowpox, MVA, NYVAC, avipox, canarypox, or fowlpox.

Permissible adjuvant set in the pharmaceutically acceptable carrier

The immunogenic composition further includes an adjuvant selected from aluminium hydroxide, aluminium phosphate, potassium aluminium sulfate, calcium phosphate hydroxide, Freund's complete adjuvant, Freund's incomplete adjuvant, iscoms, or iscomatrix.

D13L deletion as an attenuation/increased immunogenicity feature

The immunogenic composition in which the gene encoding an endogenous essential assembly or maturation protein and/or that increases immunogenicity is a poxvirus D13L gene.

Multi-gene deletion including D13L, A39R, and B37R-B8R

An immunogenic composition in which an attenuated poxvirus genome contains specific deletions in the poxvirus D13L, A39R, and B37R-B8R genes.

Administration to induce protective immune responses against specified infections

A method involving administering the immunogenic composition to induce a protective immune response in a subject against chikungunya and smallpox virus infection, smallpox and Zika virus infection, and/or chikungunya, smallpox and Zika virus infection.

The claim coverage centers on immunogenic compositions using an attenuated poxvirus vector engineered to encode chikungunya 26S subgenomic polyprotein and/or Zika PrME polyprotein, combined with deletion of endogenous essential assembly or maturation genes and/or genes that increase immunogenicity. Dependent claims further narrow the vector selection, carrier adjuvant options, and specific deletion targets, including D13L and B7R-B8R, and specify administration to induce protective immune responses against defined virus infections.

Stated Advantages

Raises protective immune responses against chikungunya, Zika, and/or smallpox.

Documented Applications

Inducing a protective immune response in a subject against chikungunya and smallpox virus infection, smallpox and Zika virus infection, and/or chikungunya, smallpox and Zika virus infection.

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