PREVENTION OF RECURRENT VIRAL DISEASE
The present invention discloses compositions and methods for ameliorating or reducing recurrent viral disease, which compositions and methods result in an increase in virus specific immunoglobulin subclasses reflective of a preferential Th1 response.
1 . A method of ameliorating symptoms of recurrent viral disease in an animal infected with a Herpes Simplex Virus, said method comprising:
identifying at least one immunogenic protein from a Herpes Simplex Virus capable of producing a predominantly T Helper Cell type 1 (Th1) immune response in an animal; and
administering said at least one immunogenic protein to an animal infected with a Herpes Simplex Virus.
2 . The method of claim 1 , wherein said Herpes Simplex Virus is Herpes Simplex Virus-2.
3 . The method of claim 2 , wherein said at least one immunogenic protein is selected from any Herpes Simplex 2 viral protein not including ICP10PK.
4 . The method of claim 1 , wherein said Herpes Simplex Virus is Herpes Simplex Virus 1.
5 . The method of claim 4 , wherein said at least one immunogenic protein is selected from any Herpes Simplex 1 viral protein not including ICP6PK.
6 . The method of claim 1 , wherein the Th1 response comprises an increase in the virus specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio from pre-administration levels.
7 . The method of claim 1 , wherein the Th1 response comprises an increase in interleukin-12 (IL-12) levels from pre-administration levels.
8 . The method of claim 1 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses from pre-administration levels.
9 . The method of claim 8 , wherein said increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses is selected from the group consisting of IgG2a/IgG1, IgG1/IgG4, IgG2/IgG4, IgG3/IgG4, (IgG1+IgG2+IgG3)/IgG4, (IgG1+IgG2+IgG3)/IgG5, IgG1/IgE, IgG2/IgE and IgG3/IgE.
10 . The method of claim 1 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses, an increase in the viral specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio, an increase in the CD8+CTL levels, and an increase in the IL-12 levels, by at least 25% each from pre-administration levels.
11 . The method of claim 1 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses by at least 25% from pre-administration levels.
12 . The method of claim 1 , wherein the Th1 response comprises an increase in viral specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio, by at least 25% from pre-administration levels.
13 . The method of claim 1 , wherein the Th1 response comprises an increase in CD8+CTL levels, by at least 25% from pre-administration levels.
14 . The method of claim 1 , wherein the Th1 response comprises an increase in IL-12 levels, by at least 25% from pre-administration levels.
15 . The method of claim 1 , wherein the amelioration of symptoms includes decreasing frequency of reactivation of latent virus.
16 . The method of claim 1 , wherein the amelioration of symptoms includes decreasing frequency of recurrent disease.
17 . A method of ameliorating symptoms of a recurrent viral disease in an animal infected with a latently infecting Herpes Simplex Virus, the method comprising:
identifying at least a portion of a Herpes Simplex Virus mutant capable of producing a predominantly Th1 immune response in an animal;
administering said at least portion of a Herpes Simplex Virus mutant to an animal infected with a latently infecting Herpes Simplex Virus.
18 . The method of claim 17 , wherein said at least a portion of a Herpes Simplex Virus mutant is modified to induce a T Helper Cell type 1 (Th1) immune response.
19 . The method of claim 17 , wherein said at leak a portion of a Herpes Simplex Virus mutant has a reduced capability of eliciting a Th2 response compared to a wild type Herpes Simplex Virus.
20 . The method of claim 17 , wherein said at least a portion of a Herpes Simplex Virus mutant is modified to induce a T Helper Cell type 1 (Th1) immune response as compared to a T Helper Cell type 2 (Th2) immune response.
21 . The method of claim 17 , wherein said Herpes Simplex Virus is Herpes Simplex Virus-2.
22 . The method of claim 21 , wherein said Herpes Simplex Virus mutant is an ICP10ΔPK virus.
23 . The method of claim 17 , wherein said Herpes Simplex Virus is Herpes Simplex Virus-1.
24 . The method of claim 23 , wherein said Herpes Simplex Virus mutant is an ICP6ΔPK virus.
25 . The method of claim 17 , wherein said animal is a human.
26 . The method of claim 17 , wherein the Th1 response comprises an increase in virus specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio from pre-administration levels.
27 . The method of claim 17 , wherein the Th1 response comprises an increase in interleukin-12 (IL-12) levels from pre-administration levels.
28 . The method of claim 17 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses from pre-administration levels
29 . The method of claim 28 , wherein said increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses is selected from the group consisting of IgG2a/IgG1, IgG1/IgG4, IgG2/IgG4, IgG3/IgG4, (IgG1+IgG2+IgG3)/IgG4, (IgG1+IgG2+IgG3)/IgG5, IgG1/IgE, IgG2/IgE and IgG3/IgE.
30 . The method of claim 17 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses, an increase in the viral specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio, an increase in the CD8+CTL levels, and an increase in the IL-12 levels, by at least 25% each from pre-administration levels.
31 . The method of claim 17 , wherein the Th1 response comprises an increase in the ratio of virus specific Th1 preferential immunoglobulin subclasses by at least 25% from pre-administration levels.
32 . The method of claim 17 , wherein the Th1 response comprises an increase in the viral specific interferon γ/interleukin-10 (IFNγ/IL-10) ratio, by at least 25% from pre-administration levels.
33 . The method of claim 17 , wherein the Th1 response comprises an increase in the CD8+CTL levels, by at least 25% from pre-administration levels.
34 . The method of claim 17 , wherein the Th1 response comprises an increase in the IL-12 levels, by at least 25% from pre-administration levels.
35 . The method of claim 17 , wherein the amelioration of symptoms includes decreasing frequency of reactivation of latent virus.
36 . The method of claim 17 , wherein the amelioration of symptoms includes decreasing frequency of recurrent disease.
37 . A method of ameliorating symptoms of recurrent viral disease in an animal infected with a Herpes Simplex Virus, said method comprising:
identifying at least one immunogenic protein from a Herpes Simplex Virus capable of producing a predominantly T Helper Cell type 1 (Th1) immune response in an animal; and
administering a nucleic acid encoding said at least one immunogenic protein to an animal infected with a Herpes Simplex Virus.