Immunization of avians by administration of non-replicating vectored vaccines

Abstract

The present invention relates generally to the fields of immunology and vaccine technology. More specifically, the invention relates to recombinant human adenovirus vectors for delivery of avian immunogens and antigens, such as avian influenza into avians. The invention also provides methods of introducing and expressing an avian immunogen in avian subjects, including avian embryos, as well as methods of eliciting an immunogenic response in avian subjects to avian immunogens.

1 . A recombinant human adenovirus expression vector that comprises and expresses an adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest.  
     
     
         2 . The expression vector according to  claim 1 , wherein the adenoviral DNA sequence is derived from adenovirus serotype 5 (Ad5).  
     
     
         3 . The expression vector according to  claim 1 , wherein the adenoviral DNA sequence is selected from the group consisting of replication-defective adenovirus, non-replicating adenovirus, replication-competent adenovirus, or wild-type adenovirus.  
     
     
         4 . The expression vector according to  claim 1 , wherein the promoter sequence is selected from the group consisting of viral promoters, avian promoters, CMV promoter, SV40 promoter, β-actin promoter, albumin promoter, Elongation Factor 1-α (EF1-α) promoter, PγK promoter, MFG promoter, or Rous sarcoma virus promoter.  
     
     
         5 . The expression vector according to  claim 1 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         6 . The expression vector according to  claim 5 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from one or more avian viruses.  
     
     
         7 . The expression vector according to  claim 5 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza.  
     
     
         8 . The expression vector of  claim 7 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         9 . The expression vector of  claim 7 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         10 . An immunogenic composition or vaccine for in vivo delivery into an avian subject comprising a veterinarily acceptable vehicle or excipient and a recombinant human adenovirus expression vector that comprises and expresses an adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest.  
     
     
         11 . The immunogenic composition or vaccine of  claim 10 , wherein the adenoviral DNA sequence is derived from adenovirus serotype 5 (Ad5).  
     
     
         12 . The immunogenic composition or vaccine of  claim 10 , wherein the adenoviral DNA sequence is selected from the group consisting of replication-defective adenovirus, non-replicating adenovirus, replication-competent adenovirus, or wild-type adenovirus.  
     
     
         13 . The immunogenic composition or vaccine of  claim 10 , wherein the promoter sequence is selected from the group consisting of viral promoters, avian promoters, CMV promoter, SV40 promoter, β-actin promoter, albumin promoter, Elongation Factor 1-α (EF1-α) promoter, PγK promoter, MFG promoter, or Rous sarcoma virus promoter.  
     
     
         14 . The immunogenic composition or vaccine of  claim 10 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         15 . The immunogenic composition or vaccine of  claim 10 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from one or more avian viruses.  
     
     
         16 . The immunogenic composition or vaccine of  claim 10 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza.  
     
     
         17 . The immunogenic composition or vaccine of  claim 16 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         18 . The immunogenic composition or vaccine of  claim 17 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3 or 5.  
     
     
         19 . The composition or vaccine of  claim 10 , further comprising an adjuvant.  
     
     
         20 . The composition or vaccine of  claim 10 , further comprising an additional vaccine.  
     
     
         21 . A method of introducing and expressing one or more avian antigens or immunogens in a cell, comprising contacting the cell with a recombinant human adenovirus expression vector that comprises and expresses an adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest, and culturing the cell under conditions sufficient to express the one or more avian antigens or immunogens in the cell.  
     
     
         22 . The method of  claim 21 , wherein the cell is a 293 cell.  
     
     
         23 . The method of  claim 21 , wherein the cell is a PER.C6 cell.  
     
     
         24 . The method of  claim 21 , wherein the one or more avian antigens or immunogens of interest are derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         25 . The method of  claim 24 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from one or more avian viruses.  
     
     
         26 . The method of  claim 24 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza.  
     
     
         27 . The method of  claim 26 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         28 . The method of  claim 27 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         29 . A method of introducing and expressing one or more avian influenza antigens or immunogens in an avian embryo, comprising contacting the avian embryo with a recombinant human adenovirus expression vector that comprises and expresses an adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest, thereby obtaining expression of the one or more avian influenza antigens or immunogens in the avian embryo.  
     
     
         30 . The method of  claim 29 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from one or more avian viruses.  
     
     
         31 . The method of  claim 29 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza.  
     
     
         32 . The method of  claim 31 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         33 . The method of  claim 32 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         34 . The method of  claim 29  further comprising administering an additional vaccine.  
     
     
         35 . The method of  claim 29 , wherein the contacting occurs by in ovo delivery.  
     
     
         36 . A method of eliciting an immunogenic response in an avian subject, comprising administering an immunologically effective amount of the composition of any one of claims  10 - 20  to the avian subject.  
     
     
         37 . A method of eliciting an immunogenic response to avian influenza in an avian subject, comprising administering an immunologically effective amount of the composition of any one of claims  10 - 20  to the avian subject.  
     
     
         38 . A method of eliciting an immunogenic response in an avian subject, comprising infecting the avian subject with an immunologically effective amount of an immunogenic composition comprising a recombinant human adenovirus expression vector that comprises and expresses an adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest, wherein the one or more avian antigens or immunogens of interest are expressed at a level sufficient to elicit an immunogenic response to the one or more avian antigens or immunogens of interest in the avian subject.  
     
     
         39 . The method of  claim 38 , wherein the one or more avian antigens or immunogens of interest are derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         40 . The method of  claim 39 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza.  
     
     
         41 . The method of  claim 40 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         42 . The method of  claim 41 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         43 . The method of  claim 38  further comprising an additional vaccine.  
     
     
         44 . The method of  claim 38 , wherein the avian subject is infected by intramuscular injection of the wing-web, wing-tip, pectoral muscle, or thigh musculature.  
     
     
         45 . The method of  claim 38 , wherein the avian subject is infected in ovo.  
     
     
         46 . A method for inoculation of an avian subject, comprising in ovo administration of a recombinant human adenovirus containing and expressing an heterologous nucleic acid molecule encoding an antigen of a pathogen of the avian subject.  
     
     
         47 . The method of  claim 46 , wherein the human adenovirus comprises sequences derived from adenovirus serotype 5.  
     
     
         48 . The method of  claim 46 , wherein the human adenovirus comprises sequences derived from replication-defective adenovirus, non-replicating adenovirus, replication-competent adenovirus, or wild-type adenovirus.  
     
     
         49 . The method of  claim 46 , wherein the antigen of a pathogen of the avian is derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         50 . The method of  claim 49 , wherein the antigen of a pathogen of the avian is derived from avian influenza.  
     
     
         51 . The method of  claim 50 , wherein the avian influenza antigens or immunogens are selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         52 . The method of  claim 50 , wherein the avian influenza antigens or immunogens are selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         53 . The method of  claim 46  further comprising administering an additional vaccine.  
     
     
         54 . An in ovo administration apparatus for delivery of an immunogenic composition to an avian embryo wherein the apparatus contains a recombinant human adenovirus expression vector expressing one or more avian antigens or immunogens of interest, wherein the apparatus delivers to the recombinant human adenovirus to the avian embryo.  
     
     
         55 . The apparatus of  claim 54 , wherein the human adenovirus expression vector comprises sequences derived from adenovirus serotype 5.  
     
     
         56 . The apparatus of  claim 54 , wherein the human adenovirus expression vector comprises sequences derived from replication-defective adenovirus, non-replicating human adenovirus, replication-competent adenovirus, or wild-type adenovirus.  
     
     
         57 . The apparatus of  claim 54 , wherein the one or more avian antigens or immunogens of interest are derived from avian influenza virus, infectious bursal disease virus, Marek's disease virus, avian herpesvirus, infectious laryngotracheitis virus, avian infectious bronchitis virus, avian reovirus, avipox, fowlpox, canarypox, pigeonpox, quailpox, and dovepox, avian polyomavirus, Newcastle Disease virus, avian pneumovirus, avian rhinotracheitis virus, avian reticuloendotheliosis virus, avian retroviruses, avian endogenous virus, avian erythroblastosis virus, avian hepatitis virus, avian anemia virus, avian enteritis virus, Pacheco's disease virus, avian leukemia virus, avian parvovirus, avian rotavirus, avian leukosis virus, avian musculoaponeurotic fibrosarcoma virus, avian myeloblastosis virus, avian myeloblastosis-associated virus, avian myelocytomatosis virus, avian sarcoma virus, or avian spleen necrosis virus.  
     
     
         58 . The method of  claim 57 , wherein the one or more avian antigens or immunogens of interest are derived from avian influenza.  
     
     
         59 . The method of  claim 58 , wherein the avian influenza antigens or immunogens are selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.  
     
     
         60 . The method of  claim 58 , wherein the avian influenza antigens or immunogens of interest is selected from the group consisting of hemagglutinin subtype 3, 5, 7, or 9.  
     
     
         61 . The method of  claim 58  further comprising administering an additional vaccine.  
     
     
         62 . A method of immunizing an avian host comprising inoculation of a non-replicating expression vector that encodes one or more pathogen-derived antigens.