Recombinant live vaccine based on canine herpesvirus, in particular against Carre's disease, rabies or the parainfluenza virus type 2.

Abstract

Disclosed and claimed is a recombinant canine herpes virus (CHV). The recombinant CHV includes and expresses at least one heterologous nucleotide sequence encoding an antigen. The antigen can be canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F, Borrelia burgdorferi OspA, or Borrelia burgdorferi OspB. The at least one heterologous nucleotide sequence can be in at least one insertion site selected from the group consisting of ORF3 (SEQ ID NO:4), ORF5 (SEQ ID NO:5), the thymidine kinase gene, and the intergenic region corresponding to genes coding for the large subunit and the small subunit. Immunological or vaccine compositions as well as methods for inducing an immunological response are also disclosed and claimed.

1 - 16 . (canceled)  
     
     
         17 . A recombinant canine herpes virus (CHV) comprising and expressing at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase.  
     
     
         18 . The recombinant CHV according to  claim 17  wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB.  
     
     
         19 . The recombinant CHV of  claim 17  wherein the at least one heterologous nucleotide sequence is inserted by simple insertion, or after total or partial deletion of the insertion locus.  
     
     
         20 . The recombinant CHV according to  claim 17  further comprising a strong eukaryotic promoter; wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter.  
     
     
         21 . The recombinant CHV according to  claim 20  wherein the strong eukaryotic promoter comprises a CMV immediate-early promoter.  
     
     
         22 . The recombinant CHV of  claim 21  wherein the CMV immediate-early promoter comprises a murine or human CMV immediate-early promoter.  
     
     
         23 . The recombinant CHV according to  claim 17  comprising at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter.  
     
     
         24 . The recombinant CHV according to  claim 23  wherein the eukaryotic promoters are CMV immediate-early promoters of different animal origin.  
     
     
         25 . The recombinant CHV according to  claim 23  comprising a first heterologous nucleotide sequence operably linked to a first promoter and a second heterologous nucleotide sequence operably linked to a second promoter; wherein, the first promoter comprises a CMV immediate-early promoter, and, the first and second promoters are arranged so that their 5′ ends are adjacent.  
     
     
         26 . The recombinant CHV according to  claim 18  further comprising at least one heterologous nucleotide sequence encoding an immunomodulatory polypeptide.  
     
     
         27 . The recombinant CHV according to  claim 25  wherein the heterologous nucleotide sequence comprises a nucleotide sequence selected from the group consisting of nucleotide sequences encoding cytokines.  
     
     
         28 . The recombinant CHV according to  claim 17  wherein the heterologous nucleotide sequence comprises an expression cassette comprising from 5′ to 3′, a promoter, two or more coding regions separated in pairs by an internal ribosome entry site (IRES), and a polyadenylation signal.  
     
     
         29 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the canine distemper virus HA antigen.  
     
     
         30 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the canine distemper virus F antigen.  
     
     
         31 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the rabies virus G antigen.  
     
     
         32 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the canine parvovirus VP2 antigen.  
     
     
         33 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 HA antigen.  
     
     
         34 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 F antigen.  
     
     
         35 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspA antigen.  
     
     
         36 . The recombinant CHV of  claim 18  comprising and expressing at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspB antigen.  
     
     
         37 . The recombinant CHV according to  claim 17  wherein the at least one heterologous nucleotide sequence encodes an antigen.  
     
     
         38 . The recombinant CHV according to  claim 17  wherein the at least one heterologous nucleotide sequence encodes an immunomodulatory polypeptide.  
     
     
         39 . An immunological composition comprising a recombinant CHV; wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence is inserted by simple insertion, or after total or partial deletion of the insertion locus or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase andwherein the recombinant CHV further comprises a strong eukaryotic promoter; wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV further comprises a strong eukaryotic promoter, wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter and wherein the strong eukaryotic promoter comprises a CMV immediate-early promoter orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV further comprises a strong eukaryotic promoter, wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter, wherein the strong eukaryotic promoter comprises a CMV immediate-early promoter and wherein the CMV immediate-early promoter comprises a murine or human CMV immediate-early promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter and wherein the eukaryotic promoters are CMV immediate-early promoters of different animal origin or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter and wherein the recombinant CHV comprises a first heterologous nucleotide sequence operably linked to a first promoter and a second heterologous nucleotide sequence operably linked to a second promoter, wherein, the first promoter comprises a CMV immediate-early promoter, and, the first and second promoters are arranged so that their 5′ ends are adjacent or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV further comprises at least one heterologous nucleotide sequence encoding an immunomodulatory polypeptide or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter, wherein the recombinant CHV comprises a first heterologous nucleotide sequence operably linked to a first promoter and a second heterologous nucleotide sequence operably linked to a second promoter; wherein, the first promoter comprises a CMV immediate-early promoter, and, the first and second promoters are arranged so that their 5′ ends are adjacent and wherein the heterologous nucleotide sequence comprises a nucleotide sequence selected from the group consisting of nucleotide sequences encoding cytokines or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the heterologous nucleotide sequence comprises an expression cassette comprising from 5′ to 3′, a promoter, two or more coding regions separated in pairs by an internal ribosome entry site (IRES), and a polyadenylation signal orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine distemper virus HA antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine distemper virus F antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the rabies virus G antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine parvovirus VP2 antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 HA antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 F antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspA antigen orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspB antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an immunomodulatory polypeptide.  
     
     
         40 . A multivalent immunological composition comprising, as a mixture or to be admixed, at least a first recombinant CHV and a second recombinant CHV; wherein the heterologous nucleotide sequence in the first recombinant CHV is different than the heterologous nucleotide sequence in the second recombinant CHV; wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence is inserted by simple insertion, or after total or partial deletion of the insertion locus or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase andwherein the recombinant CHV further comprises a strong eukaryotic promoter; wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV further comprises a strong eukaryotic promoter, wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter and wherein the strong eukaryotic promoter comprises a CMV immediate-early promoter orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV further comprises a strong eukaryotic promoter, wherein at least one heterologous nucleotide sequence is operably linked to the strong eukaryotic promoter, wherein the strong eukaryotic promoter comprises a CMV immediate-early promoter and wherein the CMV immediate-early promoter comprises a murine or human CMV immediate-early promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter and wherein the eukaryotic promoters are CMV immediate-early promoters of different animal origin or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter and wherein the recombinant CHV comprises a first heterologous nucleotide sequence operably linked to a first promoter and a second heterologous nucleotide sequence operably linked to a second promoter, wherein, the first promoter comprises a CMV immediate-early promoter, and, the first and second promoters are arranged so that their 5′ ends are adjacent or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV further comprises at least one heterologous nucleotide sequence encoding an immunomodulatory polypeptide or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the recombinant CHV comprises at least two heterologous nucleotide sequences inserted into at least one insertion site wherein each heterologous nucleotide sequence is under the control of a different eukaryotic promoter, wherein the recombinant CHV comprises a first heterologous nucleotide sequence operably linked to a first promoter and a second heterologous nucleotide sequence operably linked to a second promoter; wherein, the first promoter comprises a CMV immediate-early promoter, and, the first and second promoters are arranged so that their 5′ ends are adjacent and wherein the heterologous nucleotide sequence comprises a nucleotide sequence selected from the group consisting of nucleotide sequences encoding cytokines or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the heterologous nucleotide sequence comprises an expression cassette comprising from 5′ to 3′, a promoter, two or more coding regions separated in pairs by an internal ribosome entry site (IRES), and a polyadenylation signal orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine distemper virus HA antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine distemper virus F antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the rabies virus G antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the canine parvovirus VP2 antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 HA antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the parainfluenza virus type 2 F antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspA antigen orwherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase, wherein the at least one heterologous nucleotide sequence encodes an antigen selected from the group consisting of canine distemper virus HA, canine distemper virus F, rabies virus G, canine parvovirus VP2, parainfluenza virus type 2 HA, parainfluenza virus type 2 F,  Borrelia burgdorferi  OspA, and  Borrelia burgdorferi  OspB and wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence encoding the  Borrelia burgdorferi  OspB antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an antigen or wherein the recombinant CHV comprises and expresses at least one heterologous nucleotide sequence in at least one insertion site comprising an intergenic region corresponding to genes coding for the large subunit and the small subunit of ribonucleotide reductase and wherein the at least one heterologous nucleotide sequence encodes an immunomodulatory polypeptide.  
     
     
         41 . A method for inducing an immunological response in a canine comprising administering to the canine a recombinant CHV as claimed in any one of  claims 17  to  36  or  37  or  38 .  
     
     
         42 . A method for inducing an immunological response in a canine animal comprising administering to the canine an immunological composition as claimed in  claim 39 .  
     
     
         43 . A method for inducing an immunological response in a canine comprising administering to the canine an immunological composition as claimed in  claim 40 .  
     
     
         44 . The method of  claim 41  wherein the administering comprises mucosally administering a dose comprising between 10 2  and 10 5  CCID50 of the recombinant CHV.  
     
     
         45 . The method of  claim 42  wherein the administering comprises mucosally administering a dose comprising between 10 2  and 10 5  CCID50 of the recombinant CHV.  
     
     
         46 . The method of  claim 43  wherein the administering comprises mucosally administering a dose comprising between 10 2  and 10 5  CCID50 of the recombinant CHV.  
     
     
         47 . A method for expressing a polypeptide comprising contacting a suitable cell with a recombinant CHV as claimed in any one of  claims 17  to  36  or  37  or  38 .