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).
1. A method of inducing a therapeutic innate immune response against a coronavirus in a mammalian subject in need thereof, comprising selecting a mammalian subject in need of reduced severity of coronavirus infection as the mammalian subject in need of the therapeutic innate immune response against coronavirus:
administering intranasally to the mammalian subject at least 10 8 viral particles (vp) of an E1 and E3 deleted human adenovirus, without encoding any heterologous antigen to the adenovirus,
wherein the at least 10 8 viral particles (vp) administered intranasally is an effective amount for inducing the therapeutic innate immune response against the coronavirus in the mammalian subject.
2. The method of claim 1 , wherein the therapeutic innate immune response begins within about twenty-four hours of intranasal administration and lasts at least about 21 days, whereby the method is a method of inducing a therapeutic innate immune response in an mammalian subject in need thereof within about twenty-four hours of intranasal administration that lasts at least about 21 days.
3. The method of claim 1 , wherein the coronavirus is a severe acute respiratory syndrome-associated coronavirus.
4. The method of claim 1 , wherein the therapeutic innate immune response begins within twenty-four hours of intranasal administration, whereby the method is a method of inducing a therapeutic innate immune response within 24 hours of intranasal administration.
5. The method of claim 1 , wherein the therapeutic innate immune response lasts about 47 days, whereby the method is a method of inducing a therapeutic innate immune response that lasts about 47 days.
6. The method of claim 1 , wherein the subject in need thereof is an adult, whereby the method is a method of inducing a therapeutic innate immune response in an adult mammalian subject in need thereof.
7. The method of claim 1 , wherein the at least 10 8 vp of the E1 and E3 deleted human adenovirus is administered to the mammalian subject prior to exposure to the severe acute respiratory syndrome-associated coronavirus, whereby the method is a method of inducing a therapeutic innate immune response against a severe acute respiratory syndrome-associated coronavirus in a mammalian subject in need thereof prior to exposure to the severe acute respiratory syndrome-associated coronavirus.
8. The method of claim 1 , wherein the at least 10 8 vp of the E1 and E3 deleted human adenovirus is administered to the mammalian subject post exposure to the severe acute respiratory syndrome-associated coronavirus, whereby the method is a method of inducing a therapeutic innate immune response against a severe acute respiratory syndrome-associated coronavirus in a mammalian subject in need thereof after exposure to the severe acute respiratory syndrome-associated coronavirus.
9. The method of claim 1 , wherein the at least 10 8 vp of the E1 and E3 deleted human adenovirus induces a mucosal innate immune response, whereby the method is a method of inducing a therapeutic innate immune response and a mucosal innate immune response against a severe acute respiratory syndrome-associated coronavirus in a mammalian subject in need thereof.
10. The method of claim 1 , wherein the at least 10 8 vp of the E1 and E3 deleted human adenovirus is at least 10 9 vp of E1 and E3 deleted human adenovirus or at least 10 10 vp of E1 and E3 deleted human adenovirus.
11. The method of claim 1 , wherein the coronavirus is a common cold virus.