Recombinant modified vaccinia virus ankara (MVA) equine encephalitis virus vaccine
Inventors
Steigerwald, Robin • Kalla, Markus
Assignees
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Publication Number
US-11571471-B2
Publication Date
2023-02-07
Expiration Date
Abstract
The present invention relates to recombinant modified vaccinia virus Ankara (MVA) and to methods of using the same. In particular, the invention relates to recombinant MVA comprising a nucleotide sequence encoding for a structural protein of an equine encephalitis virus (EEV) excluding encoding for a capsid protein of the EEV, a composition in particular a pharmaceutical composition, a vaccine or kit comprising the recombinant MVA, uses and methods thereof e.g., suitable for treating and/or preventing a western, Venezuelan, and/or eastern equine encephalitis virus caused disease.
Core Innovation
The recombinant modified vaccinia virus Ankara (MVA) vaccine concept is based on recombinant MVA vectors that express structural polyproteins from Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, and Western equine encephalitis virus. For each equine encephalitis virus structural polyprotein, the nucleotide sequence encoding the capsid protein is excluded.
Expression is driven by a poxvirus promoter, including Pr13.5 or PrHyb, operably linked to each of the respective nucleotide sequences encoding the structural polyproteins. The construct is configured as a multivalent single-vector format across WEEV, VEEV, and EEV.
The specification recasts the construct into product formats such as pharmaceutical composition, vaccine, and kit formats with prime/boost containers. The described results include antigen expression and neutralizing antibody findings, together with survival protection and cross-protection in lethal murine intranasal challenge.
Claims Coverage
The available claims center on one independent claim covering a recombinant MVA that carries three poxvirus-promoter-driven expression cassettes for equine encephalitis virus structural polyproteins, with capsid protein exclusion for each virus. Dependent features further define promoter choices, sequence identifiers, insertion loci, and vaccine format.
Triple poxviral-promoter-driven structural polyprotein expression with capsid exclusion
A recombinant modified vaccinia virus Ankara (MVA) comprising: a poxviral promoter operably linked to a first nucleotide sequence encoding a structural polyprotein of an Eastern equine encephalitis virus, wherein the nucleotide sequence encoding the capsid protein for said virus is excluded; a poxviral promoter operably linked to a second nucleotide sequence encoding a structural polyprotein of a Venezuelan equine encephalitis virus, wherein the nucleotide sequence encoding the capsid protein for said virus is excluded; and a poxviral promoter operably linked to a third nucleotide sequence encoding a structural polyprotein of a Western equine encephalitis virus, wherein the nucleotide sequence encoding the capsid protein for said virus is excluded.
Defined structural polyprotein sequence identifiers
The recombinant MVA where the first nucleotide sequence encoding the structural polyprotein corresponds to SEQ ID NO: 4, the second nucleotide sequence corresponds to SEQ ID NO: 5, and the third nucleotide sequence corresponds to SEQ ID NO: 6.
Selected poxviral promoter choices (Pr13.5 or PrHyb)
The recombinant MVA where at least one poxviral promoter is selected from Pr13.5 and PrHyb.
First expression cassette insertion at MVA intergenic region IGR 44/45
The recombinant MVA where the first operably linked nucleotide sequence is inserted into the MVA intergenic region (IGR) 44/45.
Second and third expression cassettes insertion at MVA intergenic region IGR 88/89
The recombinant MVA where the second and third nucleotide sequences are inserted into the MVA intergenic region (IGR) 88/89.
Vaccine comprising the recombinant MVA
A vaccine comprising the recombinant MVA.
Coverage centers on a multivalent recombinant MVA that expresses Eastern, Venezuelan, and Western equine encephalitis virus structural polyproteins under poxviral promoters while excluding each virus capsid protein. Dependent elements further constrain promoter selection, sequence identifiers, and insertion loci in the MVA genome, and recast the construct as a vaccine.
Stated Advantages
Survival protection and cross-protection in lethal murine intranasal challenge are described in the specification.
Antigen expression and neutralizing antibodies are described in the specification.
Documented Applications
Lethal murine intranasal challenge in BALB/c mice is described, including survival protection and cross-protection.
A vaccine and a pharmaceutical composition are described as product formats incorporating the recombinant MVA.
Kit formats with prime/boost containers are described.
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