Noninvasive genetic immunization, expression products therefrom, and uses thereof

Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, ...

SYSTEM FOR RAPID PRODUCTION OF HIGH-TITER AND REPLICATION-COMPETENT ADENOVIRUS-FREE RECOMBINANT ADENOVIRUS VECTORS

The present invention relates generally to the fields of gene therapy, immunology, and vaccine technology. More specifically, the invention relates to a novel system that can rapidly generate high titers of adenovirus vectors that are free of replication-competent adenovirus (RCA). Also provided are methods of generating these RCA-free adenoviral vectors, immunogenic or vaccine compositions comprising these RCA-free adenovirus vectors, methods of expressing a heterologous nucleic acid of interest in these adenovirus vectors and methods of eliciting immunogenic responses using these adenovirus vectors.

Noninvasive genetic immunization, expression products therefrom and uses thereof

Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, tetanus toxin C-fragment, anthrax protective antigen, HIV gp 120, human carcinoembryonic antigen, and/or a therapeutic, an immunomodulatory gene, such as co-stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector.

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 contacting the avian embryo with 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 , 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 claim 1 , infectious bursal disease virus claim 1 , Marek's disease virus claim 1 , avian herpesvirus claim 1 , infectious laryngotracheitis virus claim 1 , avian infectious bronchitis virus claim 1 , avian reovirus claim 1 , avipox claim 1 , fowlpox claim 1 , canarypox claim 1 , pigeonpox claim 1 , quailpox claim 1 , and dovepox claim 1 , avian polyomavirus claim 1 , Newcastle Disease virus claim 1 , avian pneumovirus claim 1 , avian rhinotracheitis virus claim 1 , avian reticuloendotheliosis virus claim 1 , avian retroviruses claim 1 , avian endogenous virus claim 1 , avian erythroblastosis virus claim 1 , ...

RAPID AND PROLONGED IMMUNOLOGIC-THERAPEUTIC

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT). 1. A method for generating an immune response against an anthrax infection in a mammalian subject in need thereof comprising:{'i': Bacillus anthracis', 'Bacillus anthracis, 'sup': '7', 'administering intranasally, during a period within 1-2 days before exposure to , an effective amount of at least 10infectious units (ifu) of E1 and/or E3 deleted adenovirus that contains and expresses a antigen codon optimized for the mammalian subject,'}{'i': 'Bacillus anthracis', 'wherein a protective response against the antigen begins within twenty four hours of administration providing treatment to the subject at risk of the anthrax infection.'}2Bacillus anthracis. The method of claim 1 , wherein the antigen is protective antigen.3Bacillus anthracis. The method of claim 1 , wherein the antigen is lethal factor.4. The method of claim 1 , wherein the effective amount is at least 10infectious units (ifu) of E1 and/or E3 deleted adenovirus.5. The method of claim 1 , wherein the effective amount is at least 10infectious units (ifu) of E1 and E3 deleted or disrupted adenovirus.6. The method of claim 1 , wherein the effective amount is at least 10infectious units ( ...

Vaccine and drug delivery by topical application of vectors and vector extracts

Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response. 1B. anthracis. A non-invasive method of inducing a protective immune response to in a mammal , comprising:{'i': B. anthracis', 'B. anthracis, 'administering to the mammal a non-replicating adenoviral vector that contains and expresses one or more protective antigen, one or more lethal factor, or a combination thereof, to a mucosal region of the mammal.'}2. The method of claim 1 , wherein the adenoviral vector is defective in its E1 and/or E3 and/or E4 regions.3. The method of claim 1 , wherein the adenoviral vector is defective in its E1/E3 region.4. The method of claim 1 , wherein the adenoviral vector is defective in all adenoviral genes.5. The method of claim 1 , wherein administering to the mucosal region comprises intranasal or oral administration.6. The method of claim 1 , further comprising administering an adjuvant.7. A non-invasive method of inducing a protective immune response to influenza in an animal claim 1 , comprising:administering, to the animal a non-replicating adenoviral vector that contains and expresses one or more influenza antigens, one or more influenza epitopes, or a combination thereof, to a mucosal region of the animal.8. The method of claim 7 , wherein the adenoviral vector is defective in its E1 and/or E3 and/or E4 regions.9. The method of claim 7 , wherein the adenoviral vector is defective in its E1/E3 region.10. The method of claim 7 , wherein the adenoviral vector is defective in all adenoviral genes.11. The method of claim 7 , wherein administering to the mucosal region comprises intranasal or ...

RAPID AND PROLONGED IMMUNOLOGIC-THERAPEUTIC

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT). 1. A method for inducing a rapid and prolonged protective response against respiratory pathogens in a mammalian subject in need thereof comprising administering intranasally an effective amount of at least 10infectious units (ifu) of an empty E1 and/or E3 deleted adenovirus vector , without encoding a pathogen-derived antigen , wherein the protective response begins within about twenty four hours of administration and lasts at least 21 days.2. The method of claim 1 , wherein the respiratory pathogen is a virus.3. The method of claim 2 , wherein the virus is a othomyxovirus claim 2 , a paramyxovirus claim 2 , a rhinovirus or a coronavirus.4. The method of claim 2 , wherein the virus is an influenza virus claim 2 , a respiratory syncytial virus (RSV) claim 2 , a common cold virus or a measles virus.5. The method of claim 4 , wherein the common cold virus is a rhinovirus or a coronavirus.6. The method of claim 1 , wherein the respiratory pathogen is a bacterium.7Bacillus, Mycobacterium, Staphylococcus, Streptococcus, Pseudomonas, Klebsiella, HaemophilusMycoplasma.. The method of claim 6 , wherein the bacterium is selected from the group consisting ...

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.

RAPID AND PROLONGED IMMUNOGENIC-THERAPEUTIC

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT). 119-. (canceled)20. A pharmaceutical formulation suitable for a single dose intranasal administration to a mammalian subject , comprising:{'sup': '7', 'an effective amount of at least 10infectious units (ifu) of E1 and/or E3 defective adenovirus vector that contains and expresses influenza virus hemagglutinin antigen codon optimized for the mammalian subject, wherein the effective amount induces a protective immune response within 24 hours of administration; and,'}a pharmaceutically acceptable diluent or carrier.21. The formulation of claim 20 , wherein the influenza virus is swine influenza claim 20 , seasonal influenza claim 20 , avian influenza claim 20 , influenza A type claim 20 , H1N1 influenza or H5N1 influenza.22. The formulation of claim 20 , wherein the mammalian subject is a human.23. The formulation of claim 20 , wherein the adenovirus is a human adenovirus.24. The formulation of claim 20 , wherein the adenovirus is a bovine adenovirus claim 20 , a canine adenovirus claim 20 , a non-human primate adenovirus claim 20 , a chicken adenovirus claim 20 , or a porcine or swine adenovirus.25. The formulation of claim 20 , wherein the ...

VACCINE AND DRUG DELIVERY BY INTRANASAL APPLICATION OF VECTOR AND VECTOR EXTRACTS

Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response. 110-. (canceled)11. A pharmaceutical dosage for intranasal administration , comprising:a pharmaceutical acceptable carrier in a liquid form admixed with a non-replicating adenoviral vector that expresses one or more influenza antigens, one or more influenza epitopes, or a combination thereof, wherein the vector is configured to non-invasively induce a protective immune response against influenza.12. The pharmaceutical dosage of claim 11 , further comprising a squeeze spray dispenser claim 11 , a pump dispenser claim 11 , or an aerosol dispenser.13. The pharmaceutical dosage of claim 11 , wherein the adenoviral vector is defective in its E1 and/or E3 and/or E4 regions.14. The pharmaceutical dosage of claim 11 , wherein the adenoviral vector is defective in its E1/E3 region.15. The pharmaceutical dosage of claim 11 , wherein the adenoviral vector is defective in all adenoviral genes.16. The pharmaceutical dosage of claim 11 , further comprising an adjuvant.17. The pharmaceutical dosage of claim 11 , wherein the influenza antigen is influenza hemagglutinin or influenza nuclear protein.18. A pharmaceutical dosage for intranasal administration claim 11 , comprising:a pharmaceutical acceptable carrier in a liquid form admixed with a non-replicating adenoviral vector that expresses one or more heterologous antigens of interest, wherein the vector is configured to non-invasively induce a protective immune response against a pathogen.19botulinummycobacterium tuberculosis. The pharmaceutical dosage of claim 18 , wherein the one or more ...

RAPID AND PROLONGED IMMUNOLOGIC-THERAPEUTIC

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT). 119-. (canceled)20. A method of inducing an innate immune response against respiratory pathogens including a coronavirus in a mammalian subject in need thereof , comprising:selecting a mammalian subject in need of reduced severity of infection by the respiratory pathogens as the mammalian subject in need of the innate immune response,{'sup': '8', 'administering intranasally to the mammalian subject a formulation comprising an intranasal dose of at least 10viral particles (vp) of an E1 and E3 deleted human adenovirus vector that expresses a coronavirus antigen transgene,'}{'sup': '8', 'wherein the at least 10viral particles (vp) administered intranasally is an effective amount for inducing the innate immune response against the respiratory pathogens in the mammalian subject, and'}wherein the innate immune response comprises an immune response independent of the transgene.21. The method of claim 20 , wherein the coronavirus is a severe acute respiratory syndrome-associated virus.22. The method of claim 20 , wherein the coronavirus is a common cold virus.23. The method of claim 20 , comprising administering at least 10viral particles (vp) of E1 and ...

Rapid and prolonged immunogic therapeutic

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Rapid and prolonged immunogic therapeutic

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Immunizations 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.

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.

Rapid and prolonged immunologic therapeutic

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Immunization of avians by mucosal 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 mucosal administration via aerosol spray to avians of immunogenic and vaccine compositions, including those comprising recombinant human adenovirus vectors for delivery of genes encoding avian immunogens or antigens, such as genes encoding avian influenza virus. The invention also provides methods and apparatus for use in such administration.

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.

Noninvasive genetic immunization, expression products therefrom, and uses thereof.

Noninvasive Genetic Immunization, Expression Products Therefrom, and Uses Thereof

Intranasal administration of an adenovirus vector to induce a protective immune response to an inhalation pathogen

The present invention shows that intranasal administration of E1/E3 -defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the El/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3 -defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Noninvasive genetic immunization, expression products therefrom, and uses thereof

Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vectorin an amount effective to induce the system immune or therapeutic response in animals.

Noninvasive genetic immunization, expression products therefrom, and uses thereof

Noninvasive genetic immunization, expression products therefrom, and uses thereof

Abstract Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vectorin an amount effective to induce the system immune or therapeutic response in animals.

Long-acting and fast-acting immune therapeutic agent

Una composición para su uso en un método para inducir una respuesta inmunoprotectora rápida y prolongada contra el ántrax en un sujeto mamífero que lo necesite, que comprende una cantidad eficaz de al menos 107 unidades infecciosas (ifu) de adenovirus con E1 y E3 eliminado que codifica un antígeno de Bacillus anthracis, en donde la composición se administra en una administración intranasal de una sola dosis, y en donde la administración da como resultado una respuesta inmunoprotectora contra el ántrax de aproximadamente un día a aproximadamente 47 días después de la administración. A composition for use in a method of inducing a rapid and prolonged immunoprotective response against anthrax in a mammalian subject in need thereof, comprising an effective amount of at least 107 infectious units (ifu) of E1 and E3 deleted adenovirus encoding a Bacillus anthracis antigen, wherein the composition is administered in a single dose intranasal administration, and wherein the administration results in an immunoprotective response against anthrax from about one day to about 47 days after administration.

Rapid and prolonged immunogic therapeutic

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Rapid and prolonged immunologic-therapeutic

The present invention shows that intranasal administration of E1/E3 -defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the El/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3 -defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).

Noninvasive genetic immunization, expression products therefrom and uses thereof

Noninvasive genetic immunization by topical application of bacterial vectors

Vaccination and vaccine and drug delivery by topical application of vectors and vector extracts recombinant vectors, and noninvasive genetic immunization, expression products therefrom and uses thereof

Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response.

Noninvasive genetic immunization by topical application of bacterial vectors

Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response.

Rapid production of adenovirus-free recombinant adenovirus vectors

System for rapid production of high-titer and replication-competent adenovirus-free recombinant adenovirus vectors

The present invention relates generally to the fields of gene therapy, immunology, and vaccine technology. More specifically, the invention relates to a novel system that can rapidly generate high titers of adenovirus vectors that are free of replication-competent adenovirus (RCA). Also provided are methods of generating these RCA-free adenoviral vectors, immunogenic or vaccine compositions comprising these RCA-free adenovirus vectors, methods of expressing a heterologous nucleic acid of interest in these adenovirus vectors and methods of eliciting immunogenic responses using these adenovirus vectors.

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.

Rapid and prolonged immunologic-therapeutic

The present invention shows that intranasal administration of E1/E3-defective adenovirus particles may confer rapid and broad protection against viral and bacterial pathogens in a variety of disease settings. Protective responses lasted for many weeks in a single-dose regimen in animal models. When a pathogen-derived antigen gene was inserted into the E1/E3-defective adenovirus genome, the antigen-induced protective immunity against the specific pathogen was elicited before the adenovirus-mediated protective response declined away, thus conferring rapid, prolonged, and seamless protection against pathogens. In addition to E1/E3-defective adenovirus, other bioengineered non-replicating vectors encoding pathogen-derived antigens may also be developed into a new generation of rapid and prolonged immunologic-therapeutic (RAPIT).