Compositions and methods for inducing an enhanced immune response using poxvirus vectors
AssigneeBavarian Nordic A/S
InventorsJürgen Hausmann, Michael Wolferstätter
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Abstract
Provided herein are recombinant poxviruses comprising heterologous or native nucleic acids specifying excess double-stranded RNA (dsRNA) early in infection, which may further comprise heterologous nucleic acids encoding one or more costimulatory molecules, and/or heterologous nucleic acids encoding one or more infectious disease-associated antigens or tumor-associated antigens, as well as pharmaceutical compositions comprising such recombinant poxviruses and methods and uses thereof. The recombinant poxviruses provided herein enhance innate and adaptive immune activation in subjects compared to identical recombinant poxviruses lacking heterologous or native transcription units specifying excess early dsRNA.
Claims20
An engineered poxvirus that differs from wild-type poxvirus in comprising an additional early or immediate early poxviral promoter inserted downstream of the E3L gene and directing antisense transcription of said gene to produce an antisense RNA transcript that anneals with the sense transcript of said gene to form dsRNA that is more than 100 nucleotides in length.
A non-human host cell comprising an engineered poxvirus that differs from wild-type poxvirus in comprising an additional early or immediate early poxviral promoter inserted downstream of the E3L gene and directing antisense transcription of said gene to produce an antisense RNA transcript that anneals with the sense transcript of said gene to form dsRNA in the host cell prior to replication of the viral genome, wherein said dsRNA is more than 100 nucleotides in length.
A non-human host cell infected by an engineered poxvirus encoding E3L that comprises said poxvirus and further comprises dsRNA encoded by said E3L gene that is more than 100 nucleotides in length and is present in the host cell prior to replication of the viral genome, wherein the production of IFN-β by said host cell is increased by at least 2-fold compared to the production of IFN-β in a host cell infected with an unmodified poxvirus.
Dependencies are inferred from the claim text.