Modified plant viruses and methods of use thereof
View Patent ↗The present invention relates to modulating the nature and/or level of an immune response to a molecule. In particular, the invention relates to effecting an increase in the TH1 immune response to molecules such as, but not limited to, antigens or immunogens. The invention also relates to reducing a TH2 immune response to molecules. More particularly, the invention relates to altering the level of TH1- and TH2-associated immunoglobulins, the level of proliferation of TH1- and TH2-associated cytokines, and the level of proliferation of TH1 and TH2 cells.
1. A process of increasing the level of a TH1-type immune response to a peptide of interest in an animal comprising:
a) providing
i) a peptide of interest,
ii) a plant virus expressing a heterologous peptide on the exposed portion of the coat protein of said plant virus, which is capable of conjugating to said peptide of interest, wherein said plant virus is a cowpea mosaic virus (CPMV), and wherein said heterologous peptide comprises acidic amino acids and an equal number basic amino acids,
iii) a host animal;
b) chemically conjugating said peptide of interest to said heterologous peptide to generate a conjugate; and
c) administering said conjugate to said host animal to generate a treated animal under conditions such that the level of TH1-type immune response to said peptide of interest in said treated animal is increased relative to the level of TH1-type immune response to said peptide of interest that is not conjugated in a control animal.
2. The process of claim 1 , wherein said increased level of TH1-type immune response is selected from (a) increased level of TH1-associated immunoglobulin in said treated animal relative to the level of TH1-associated immunoglobulin in a control animal, (b) increased level of proliferation of TH1 cells from said treated animal relative to the level of proliferation of TH1 cells from a control animal, and (c) increased level of TH1-associated cytokine in said treated animal relative to the level of TH1-associated cytokine in a control animal.
3. The process of claim 2 , wherein said TH1-associated cytokine is selected from IL TNF-B and IFN-y.
4. The process of claim 1 , wherein said administering results in reducing symptoms associated with exposure of said host animal to said peptide of interest.
5. The process of claim 1 , wherein said peptide of interest is an antigen of a source selected from the group consisting of an animal pathogen and a cancer cell.
6. The process of claim 1 , wherein said acidic amino acids are selected from aspartic acid, glutamic acid, and cysteine, and said positively charged amino acids are selected from lysine, arginine, and histidine.
7. The process of claim 1 , wherein said heterologous peptide comprises a sequence of contiguous charged amino acids selected from a first sequence consisting of contiguous acidic amino acids and a second sequence consisting of contiguous basic amino acids.
8. The process of claim 7 , wherein said sequence of amino acids occurs in said heterologous peptide as a repeating sequence.
9. The process of claim 7 , wherein said heterologous sequence comprises said first and second sequences, and wherein said first sequence is contiguous with said second sequence.
10. The process of claim 9 , wherein said contiguous first and second sequences occur in said heterologous peptide as a repeating sequence.
11. The process of claim 1 , wherein said heterologous peptide comprises Asp-Glu-Gly-Lys-Gly-Lys-Gly-Lys-Gly-Lys-Asp-Glu listed as SEQ ID NO:29.
12. The process of claim 1 , wherein said administering is selected from intranasal, oral, parenteral, subcutaneous, intrathecal, intravenous, intraperitoneal, and intramuscular administration.
13. The process of claim 12 , wherein said administering further comprises administering a composition selected from immune adjuvant, cytokine, and pharmaceutical excipient.
14. The process of claim 1 , wherein said host animal is a mammal.
15. The process of claim 14 , wherein said mammal is selected from mouse and human.
16. The process of claim 1 , wherein said conjugate is immunogenic.
17. The process of claim 1 , further comprising step d) testing for an increase in the level of TH1-type immune response to said peptide of interest in said treated animal relative to the level of TH1-type immune response to said peptide of interest in a control animal.
18. The process of claim 17 , further comprising step e) observing an increase in the level of TH1-type immune response to said peptide of interest in said treated animal relative to the level of TH 1-type immune response to said peptide of interest in a control animal.
19. A process of increasing the level of a TH1-type immune response to a peptide of interest in an animal comprising:
providing a cowpea mosaic virus (VPMV) expressing a heterologous peptide on the exposed portion of the coat protein of said plant virus, which is capable of conjugating to said peptide of interest, wherein said plant virus is a cowpea mosaic virus (CPMV), chemically conjugating said peptide of interest to said heterologous peptide to generate a conjugate; and
administering said conjugate to said host animal to generate a treated animal under conditions such that the level of TH1-type immune response to said peptide of interest in said treated animal is increased relative to the level of TH1-type immune response to said peptide of interest that is not conjugated in a control animal.