Recombinant Rhabdoviruses as live-viral vaccines

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant Rhabdovirus vector that expresses a functional immunodeficiency virus envelope protein, or a subunit thereof, effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from an immunodeficiency virus.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus envelope protein, or a subunit thereof, effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from an immunodeficiency virus.

A recombinant non-segmented negative-stranded RNA virus vector comprising:

• a) a modified negative-stranded RNA virus genome that is deficient in Ψ gene;
• b) a new transcription unit that is inserted into said modified negative-stranded RNA virus genome to express heterologous nucleic acid sequences;
• and
• c) a heterologous viral nucleic acid sequence that is inserted into said new transcription unit, wherein said recombinant non-segmented negative-stranded RNA virus vector is replication competent, and said heterologous viral nucleic acid sequence encodes an antigenic polypeptide.

A method of treating a mammal infected with an immunodeficiency virus, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus envelope protein, or subunit thereof;
• b) expressing said functional immunodeficiency virus envelope protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional immunodeficiency virus envelope protein, or subunit thereof.

A method of protecting a mammal from an immunodeficiency virus infection, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus envelope protein, or subunit thereof;
• b) expressing said functional immunodeficiency virus envelope protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional immunodeficiency virus envelope protein, or subunit thereof.

A recombinant Rhabdovirus vector comprising:

• a) a modified Rhabdovirus genome;
• b) a new transcription unit inserted into the Rhabdovirus genome to express heterologous nucleic acid sequences;
• and
• c) a heterologous viral nucleic acid sequence that is inserted into said new transcription unit, wherein said recombinant Rhabdovirus vector is replication competent, and said heterologous viral nucleic acid sequence encodes HCV E1, E2, and p7 antigenic polypeptides.

A recombinant Rhabdovirus vector comprising:

• a) a modified Rhabdovirus genome;
• b) a new transcription unit inserted into the Rhabdovirus genome to express heterologous nucleic acid sequences;
• and
• c) a heterologous viral nucleic acid sequence that is inserted into said new transcription unit, wherein said recombinant Rhabdovirus vector is replication competent, and said heterologous viral nucleic acid sequence encodes an ectodomain of HCV E2 that has an amino acid deletion at its carboxy-terminus fused to a transmembrane domain and a cytoplasmic domain of human CD4, wherein a chimeric E2 antigenic polypeptide is expressed.

A recombinant Rhabdovirus vector comprising:

• a) a modified Rhabdovirus genome;
• b) a new transcription unit inserted into the Rhabdovirus genome to express heterologous nucleic acid sequences;
• and
• c) a heterologous viral nucleic acid sequence that is inserted into said new transcription unit, wherein said recombinant Rhabdovirus vector is replication competent, and said heterologous viral nucleic acid sequence encodes an ectodomain of HCV E2 that has an amino acid deletion at its carboxy-terminus fused to a transmembrane domain of human CD4 and a cytoplasmic domain of a Rhabdovirus glycoprotein wherein a chimeric E2 antigenic polypeptide is expressed.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant non-segmented negative stranded RNA virus vector that expresses a functional hepatitis C virus envelope protein, or a subunit thereof, in an amount effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated heptatits C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from a heptatits C virus.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant non-segmented negative stranded RNA virus vector that expresses a functional hepatitis C virus envelope protein, or a subunit thereof, in an amount effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• and
• c) inducing a long lasting cellular immune response thereto to protect said mammal from a heptatits C virus.

A method of treating a mammal infected with a hepatitis C virus, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional hepatitic C virus envelope protein, or subunit thereof;
• b) expressing said functional hepatitic C virus envelope protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated hepatitic C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional hepatitic C virus envelope protein, or subunit thereof.

A method of treating a mammal infected with a hepatitis C virus, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional hepatitic C virus envelope protein, or subunit thereof;
• b) expressing said functional hepatitic C virus envelope protein, or subunit thereof;
• and
• c) inducing a long lasting cellular immune response to said functional hepatitic C virus envelope protein, or subunit thereof.

A method of protecting a mammal from a hepatitis C virus infection, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional hepatitis C virus envelope protein, or subunit thereof;
• b) expressing said functional hepatitis C virus envelope protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated hepatitis C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional hepatitis C virus envelope protein, or subunit thereof.

A method of protecting a mammal from a hepatitis C virus infection, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional hepatitis C virus envelope protein, or subunit thereof;
• b) expressing said functional hepatitis C virus envelope protein, or subunit thereof;
• and
• c) inducing a long lasting cellular immune response to said functional hepatitis C virus envelope protein, or subunit thereof.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant non-segmented negative stranded RNA virus virion wherein said virion has on its surface a functional hepatitis C virus envelope protein, or a subunit thereof, effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated heptatits C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from a heptatits C virus.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant non-segmented negative stranded RNA virus virion wherein said virion has on its surface a functional hepatitis C virus envelope protein, or a subunit thereof, effective to induce an immunological response to said envelope protein;
• b) expressing said envelope protein, or the subunit thereof, in vivo;
• and
• c) inducing a long lasting cellular immune response thereto to protect said mammal from a heptatits C virus.

A method of treating a mammal infected with a hepatitis C virus, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus virion wherein said virion has on its surface a functional hepatitic C virus envelope protein, or subunit thereof;
• b) boosting said mammal by delivering an effective dose of an isolated hepatitic C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• c) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional hepatitic C virus envelope protein, or subunit thereof.

A method of protecting a mammal from a hepatitis C virus infection, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus virion wherein said virion has on its surface a functional hepatitis C virus envelope protein, or subunit thereof;
• b) boosting said mammal by delivering an effective dose of an isolated hepatitis C virus envelope protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• c) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional hepatitis C virus envelope protein, or subunit thereof.

A recombinant Rhabdovirus vector comprising:

• a) a modified Rhabdovirus genome;
• b) a new transcription unit inserted into the Rhabdovirus genome to express heterologous nucleic acid sequences;
• and
• c) a heterologous viral nucleic acid sequence that is inserted into said new transcription unit, wherein the recombinant Rhabdovirus vector is replication competent, and said heterologous viral nucleic acid sequence encodes an HIV gag antigenic polypeptide.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a recombinant non-segmented negative stranded RNA virus vector that expresses a functional immunodeficiency virus gag protein, or a subunit thereof, in an amount effective to induce an immunological response to said gag protein;
• b) expressing said gag protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated gag protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from an immunodeficiency virus.

A method of inducing an immunological response in a mammal, comprising:

• a) delivering to a tissue of said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus gag protein, or a subunit thereof, effective to induce an immunological response to said gag protein;
• b) expressing said gag protein, or the subunit thereof, in vivo;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus gag protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response thereto to protect said mammal from an immunodeficiency virus.

A method of treating a mammal infected with an immunodeficiency virus, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus gag protein, or subunit thereof;
• b) expressing said functional immunodeficiency virus gag protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus gag protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional immunodeficiency virus gag protein, or subunit thereof.

A method of protecting a mammal from an immunodeficiency virus infection, comprising:

• a) administering to said mammal a non-segmented negative-stranded RNA virus that expresses a functional immunodeficiency virus gag protein, or subunit thereof;
• b) expressing said functional immunodeficiency virus gag protein, or subunit thereof;
• c) boosting said mammal by delivering an effective dose of an isolated immunodeficiency virus gag protein, or a subunit thereof, in an adjuvant or by delivering an effective dose of a boost vaccine vector;
• and
• d) inducing a neutralizing antibody response and/or long lasting cellular immune response to said functional immunodeficiency virus gag protein, or subunit thereof.