Immunization of avians by administration of non-replicating vectored vaccines
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 method of introducing and expressing one or more avian antigens or immunogens in an avian embryo, comprising administering a recombinant human adenovirus expression vector that comprises and expresses a human adenoviral DNA sequence, and a promoter sequence operably linked to a foreign sequence encoding one or more avian antigens or immunogens of interest into an amnion-allantois space of an embryonated avian egg, thereby obtaining expression of the one or more avian antigens or immunogens in the avian embryo.
2. The method of claim 1 , wherein the adenovirus expression vector is a replication competent adenovirus (RCA) free recombinant human adenovirus expression vector.
3. The method of claim 1 , wherein the adenovirus expression vector is E1 and/or E3 defective adenovirus serotype 5 (Ad5).
4. The method of claim 1 , 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.
5. The method of claim 1 , wherein the foreign sequence encoding the one or more avian antigens or immunogens of interest is derived from avian influenza, wherein the avian influenza antigens or immunogens are selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.
6. A method for inoculation of an avian subject, comprising administration, into an amnion-allantois space of an embryonated avian egg, of a recombinant human adenovirus containing and expressing an heterologous nucleic acid molecule encoding an antigen of a pathogen of the avian subject.
7. The method of claim 6 , wherein the human adenovirus comprises sequences derived from replication-defective adenovirus, non-replicating adenovirus, replication-competent adenovirus, or wild-type adenovirus.
8. The method of claim 6 , wherein the antigen of a pathogen of the avian is derived from avian influenza, wherein the avian influenza antigens or immunogens are selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.
9. A method of inducing an immune response to avian influenza in an avian, comprising:
administering in ovo to an avian a recombinant human adenovirus expression vector expressing one or more avian influenza antigens,
wherein the administering in ovo is into the amnion-allantois space, and
wherein induction of the immune response provides protection against challenge with avian influenza virus.
10. The method of claim 9 , wherein the adenovirus expression vector expressing one or more avian influenza antigens is administered at a dose of about 1×10 8 to about 1×10 11 pfu per egg or an equivalent dose measured by ifu or an equivalent dose measured by virus particles.
11. The method of claim 9 , wherein the adenovirus expression vector expressing one or more avian influenza antigens is administered at a dose of about 5×10 10 pfu per egg or about at a dose of 2×10 8 ifu per egg or at a dose of about 3×10 10 viral particles per egg.
12. The method of claim 9 , wherein the immune response provides protection from a different influenza subtype than was administered in ovo.
13. The method of claim 9 , wherein the avian is administered a second dose of the recombinant human adenovirus expression vector expressing one or more avian influenza antigens post hatch.
14. The method of claim 13 , wherein the second dose is administered about 2-weeks to about 4-weeks post hatch.
15. The method of claim 13 , wherein the second dose is administered intra-muscularly or intranasally.
16. The method of claim 9 , wherein the avian is a chicken.
17. The method of claim 9 , wherein the one or more avian antigens are selected from the group consisting of hemagglutinin, nucleoprotein, matrix, or neuraminidase.
18. The method of claim 9 , wherein immunomodulatory molecules are co-administered with the one or more avian influenza antigens to the avian.
19. The method of claim 9 , wherein the adenovirus expression vector is E1 and/or E3 defective adenovirus serotype 5 (Ad5).