Recombinant modified vaccinia virus Ankara (MVA) multivalent filovirus immunogenic compositions and methods of use
Inventors
VOLKMANN, Ariane • Steigerwald, Robin • Hochrein, Hubertus • Dirmeier, Ulrike • Lauterbach, Henning • Hausmann, Jürgen Hausmann
Assignees
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Publication Number
US-10576141-B2
Publication Date
2020-03-03
Expiration Date
Abstract
The present invention relates to an improved filovirus vaccine comprising a recombinant modified vaccinia virus Ankara-based (MVA-based) vaccine against filovirus infection and to related products, methods and uses. Specifically, the present invention relates to genetically engineered (recombinant) MVA and FPV vectors comprising at least one heterologous nucleotide sequence encoding an antigenic determinant of a Marburg virus (MARV) or Ebola virus glycoprotein. Specifically, the invention relates to recombinant MVA comprising Ebola virus glycoprotein and virion protein 40. The invention also relates to products, methods and uses thereof as well as prime/boost regimens of MVA and genetically engineered (recombinant) FPV, e.g., suitable to induce a protective immune response in a subject.
Core Innovation
The invention relates to an improved multivalent filovirus vaccine strategy based on a recombinant MVA vector administered to induce an immune response in a subject. The recombinant MVA vector comprises multiple nucleic acids encoding immunogenic proteins from different filoviruses, including a MARV envelope glycoprotein (GP), Zaire Ebola virus (ZEBOV) envelope glycoprotein, Sudan Ebola virus (SEBOV) envelope glycoprotein, and an Ebola virus Ivory Coast nucleoprotein.
The core concept includes using the recombinant MVA vector to drive immune responses directed to both envelope glycoproteins and internal Ebola virus components. The description further covers homologous prime-boost regimens using recombinant MVA vectors and heterologous prime-boost regimens using recombinant MVA in combination with fowlpox virus (FPV), including cases where an FPV boost is paired with an MVA prime or vice versa.
The encoded antigenic determinants are associated with enhanced humoral, neutralizing, and cytotoxic CD8 T-cell responses, and the disclosure additionally describes generating filovirus-like particles in the subject. The document also characterizes vector attenuation/safety with MVA-BN and provides options for promoters and insertion regions, with embodiments that include Ebola components such as NP and virion protein 40 (VP40) in addition to GP to support the described immune outcomes.
Claims Coverage
The disclosure includes at least one independent claim defining a method that administers a recombinant MVA vector encoding multiple filovirus immunogenic proteins. One additional independent claim is not explicitly provided in the provided claims excerpt, so only the identified independent claim is analyzed here.
Recombinant MVA encoding multivalent filovirus immunogenic proteins
Administering a recombinant MVA vector comprising a first nucleic acid encoding at least one immunogenic protein of a MARV envelope glycoprotein (GP), a second nucleic acid encoding an immunogenic protein of Zaire Ebola virus (ZEBOV) envelope glycoprotein, a third nucleic acid encoding an immunogenic protein of Sudan Ebola virus (SEBOV) envelope glycoprotein, and a fourth nucleic acid encoding an immunogenic protein of Ebola virus Ivory Coast nucleoprotein to induce an immune response in a subject.
Independent claim coverage centers on inducing an immune response by administering a recombinant MVA vector that simultaneously encodes immunogenic envelope glycoprotein determinants from MARV, ZEBOV, and SEBOV, together with Ebola virus Ivory Coast nucleoprotein. Dependent claim refinements specify particular immunogen sequence embodiments and additional components such as CD40L, and clarify the desired outcome as protective immunity or protective immune response.
Stated Advantages
Induces an immune response in a subject.
Enhances humoral, neutralizing, and cytotoxic CD8 T-cell responses.
Can generate filovirus-like particles in the subject.
Can provide protective immunity or a protective immune response.
Documented Applications
Use as a vaccine method for inducing immune responses in a subject against filoviruses, including multivalent (pan-filovirus) antigenic determinant combinations, with described homologous and heterologous prime-boost regimens.
Non-human primate challenge context is documented, including protection against MARV challenge and enhanced ZEBOV responses/protection.
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