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 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,
administering intranasally to the mammalian subject a formulation comprising an intranasal dose of at least 10 8 viral particles (vp) of an E1 and E3 deleted non-human primate adenovirus vector that expresses a coronavirus antigen transgene,
wherein the at least 10 8 viral 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 E1 and E3 deleted adenovirus vector induces the innate immune response independent of the transgene.
2. The method of claim 1 , wherein the coronavirus is a severe acute respiratory syndrome-associated virus.
3. The method of claim 1 , comprising administering at least 10 9 viral particles (vp) of E1 and E3 deleted adenovirus or at least 10 10 viral particles (vp) of E1 and E3 deleted adenovirus.
4. The method of claim 1 , wherein the innate immune response lasts at least 21 days, whereby the method is a method of inducing an innate immune response against the respiratory pathogens in a mammalian subject in need thereof that lasts at least about 21 days.
5. The method of claim 1 , wherein the mammalian subject in need thereof is an adult.
6. The method of claim 1 , wherein administering intranasally the effective amount of the E1 and E3 deleted non-human primate adenovirus vector comprises administering intranasally a first dose of the E1 and E3 deleted non-human primate adenovirus vector to the mammalian subject, and administering a second dose of the E1 and E3 deleted non-human primate adenovirus vector to the mammalian subject, with the administering of the first and second doses being about 20 days apart, 25 days apart, 30 days apart, 35 days apart, 40 days apart, 41 days apart, 42 days apart, 43 days apart, 44 days apart, 45 days apart, 46 days apart, 47 days apart, 48 days apart, 49 days apart or 50 days apart.
7. The method of claim 1 , wherein the innate immune response is a mucosal immune response against the respiratory pathogens in a mammalian subject in need thereof.
8. The method of claim 1 comprising
inducing an IgA response or
inducing a humoral response in a mammalian subject in need thereof.
9. The method of claim 1 comprising inducing a cellular response in a mammalian subject in need thereof.
10. The method of claim 1 , wherein the coronavirus is a common cold virus.
11. The method of claim 1 , wherein the administering intranasally comprises administering intranasally a first dose of the E1 and E3 deleted non-human primate adenovirus vector to the mammalian subject, and administering intranasally a second dose of the E1 and E3 deleted non-human primate adenovirus vector to the mammalian subject.
12. The method of claim 1 comprising, after the administering intranasally, monitoring severity of infection or immune response of the mammalian subject.
13. A method of inducing an innate immune response in a mammalian subject in need thereof, comprising:
selecting a mammalian subject in need of the innate immune response as the mammalian subject,
administering intranasally to the mammalian subject a formulation comprising an intranasal dose of at least 10 8 viral particles (vp) of an E1 and E3 deleted non-human primate adenovirus vector that expresses a coronavirus antigen transgene,
wherein the at least 10 8 viral particles (vp) administered intranasally is an effective amount for inducing the innate immune response in the mammalian subject, and
wherein the E1 and E3 deleted adenovirus vector induces the innate immune response independent of the transgene.