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AssigneeBavarian Nordic A/S
InventorsJürgen Hausmann, Michael Wolferstätter
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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.
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A recombinant poxvirus for inducing an enhanced innate immune response, the recombinant poxvirus comprising heterologous nucleic acids generating excess double stranded RNA (dsRNA) early in infection, wherein the heterologous nucleic acids comprise sequences that encode partially or completely complementary RNA transcripts that anneal after transcription to form dsRNA, wherein the partially or completely complementary RNA transcripts overlap by 100 or more nucleotides, and wherein the dsRNA enhances an innate immune response as compared to a recombinant poxvirus comprising heterologous nucleic acids that do not express excess dsRNA early in infection.
A method for enhancing an innate immune response, the method comprising administering a recombinant poxvirus to a subject, wherein the recombinant poxvirus comprises heterologous nucleic acids generating excess double stranded RNA (dsRNA) early in infection in the subject, wherein the heterologous nucleic acids comprise sequences that encode partially or completely complementary RNA transcripts that anneal after transcription to form dsRNA, wherein the partially or completely complementary RNA transcripts overlap by 100 or more nucleotides, and wherein the dsRNA enhances the innate immune response in the subject as compared to a recombinant poxvirus comprising heterologous nucleic acids that do not express excess dsRNA early in infection.
A recombinant poxvirus for inducing an innate enhanced immune response, the recombinant poxvirus comprising a first heterologous nucleic acid and a second heterologous nucleic acid, wherein the first heterologous nucleic acid comprises sequences that encode a first RNA transcript partially or completely complementary to a second RNA transcript encoded by the second heterologous nucleic acid, wherein the first and second RNA transcripts anneal after transcription to form double stranded RNA (dsRNA) early in infection, wherein the first and second RNA transcripts overlap by 100 or more nucleotides, and wherein the dsRNA enhances an immune response as compared to a recombinant poxvirus comprising heterologous nucleic acids that do not express excess dsRNA early in infection.
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