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J-LEAPS vaccines elicit antigen specific Th1 responses by promoting maturation of type 1 dendritic cells (DC1)

1Roseman University College of Medicine, Las Vegas, NV 89135, USA
2CEL-SCI Corporation, 8229 Boone Blvd, Suite 802, Vienna VA 22182, USA

Topical Section: Dendritic Cell Control of Immune Responses

The J-LEAPS peptide vaccine platform allows development of vaccines that elicit antigen specific Th1 immune responses to the incorporated antigenic peptide by promoting the maturation of mouse and human precursors into type 1 dendritic cells (DC1). CD8 T cell epitopes are covalently attached to the J-immune cell binding ligand through a tri-glycine linker. J-LEAPS peptide vaccines have been tested in mouse models and elicit protection against lethal challenge with herpes simplex virus type 1, relevant immune responses to human immunodeficiency virus and tuberculosis, prevent the establishment of tumors and the spread of HER-2/neu tumor cells and stop the progression of autoimmune diseases such as experimental autoimmune myocarditis and rheumatoid arthritis. Importantly, adoptive transfer of DC1s matured with J-LEAPS vaccines for HSV-1 or influenza A elicits antigen specific protection from lethal infection with these viruses. J-LEAPS peptides or J-LEAPS-DCs have great potential for the development of vaccines to elicit Th1 and immunomodulatory prophylaxis and therapy for microbial diseases, cancer and select autoimmune diseases.
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References

1. Zimmerman DH, Bergmann K, Rosenthal K, et al. (1996) A new approach to T-cell activation: natural and synthetic conjugates capable of activating T cells. Vaccine Res 5: 91–102.

2. Zimmerman DH, Morris S, Rouse D, et al. (1996) Immunization with peptide heterconjugates primes a T helper cell type 1-associated antibody (IgG2a) response that recognizes the native epitope on the 38-kDA protein of Mycobacterium tuberculosis. Vaccine Res 5: 103–118.

3. Rosenthal KS (2005) Immune peptide enhancement of peptide-based vaccines. Front Biosci 10: 478–482.    

4. Goel N, Zimmerman DH, Rosenthal KS (2005) Ligand epitope presentation system vaccines against herpes simplex virus. Front Biosci 10: 966–974.    

5. Zimmerman DH, Rosenthal KS (2005) The LEAPS approach to vaccine development. Front Biosci 10: 790–798.    

6. Rosenthal KS, Taylor P, Zimmerman DH (2011) J-LEAPS Peptide and LEAPS-dendritic cell vaccines. Microb Biotechnol 5: 203–213.

7. Rosenthal KS, Mao H, Horne WI, et al. (1999) Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1. Vaccine 17: 535–542.    

8. Goel N, Rong QD, Rosenthal KS (2003) A LEAPS heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection. Vaccine 21: 4410–4420.    

9. Boonnak K, Vogel L, Orandle M, et al. (2013) Antigen-activated dendritic cells ameliorate influenza A infections. J Clin Invest 123: 2850–2861.

10. Zimmerman DH, Lloyd JD, Winship MD, et al. (2001) Induction of cross clade reactive specific antibodies in mice by conjugates of HGP-30 (peptide analog of HIV-1 (SF2) p17) and peptide segments of human beta-2-microglobulin or MHC II beta chain. Vaccine 19: 4750–4759.    

11. Zimmerman DH, Ulrich JT, Wright C, et al. (1998) Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid synthetic peptide antigen from HIV type 1 p17. Aids Res Hum Retro 14: 741–749.    

12. Rosenthal KS, Stone S, Koski G, et al. (2017) LEAPS vaccine incorporating HER-2/neu epitope elicits protection that prevents and limits tumor growth and spread of breast cancer in a mouse model. J Immunol Res 2017: 1–8.

13. Cihakova D, Barin JG, Baldeviano GC, et al. (2008) LEAPS heteroconjugate is able to prevent and treat experimental autoimmune myocarditis by altering trafficking of autoaggressive cells to the heart. Int Immunopharmacol 8: 624–633.    

14. Mikecz K, Glant TT, Markovics A, et al. (2017) An epitope-specific DerG-PG70 LEAPS vaccine modulates T cell responses and suppresses arthritis progression in two related murine models of rheumatoid arthritis. Vaccine 35: 4048–4056.    

15. Rosenthal KS, Mikecz K, Iii HLS, et al. (2015) Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis. Expert Rev Vaccines 14: 1–18.    

16. Zimmerman DH, Taylor P, Bendele A, et al. (2010) CEL-2000: a therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model. Int Immunopharmacol 10: 412–421.    

17. Parham P, Androlewicz MJ, Holmes NJ, et al. (1983) Arginine 45 is a major part of the antigenic determinant of human beta 2-microglobulin recognized by mouse monoclonal antibody BBM.1. J Biol Chem 258: 6179–6186.

18. Cammarota G, Scheirle A, Takacs B, et al. (1992) Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules. Nature 356: 799–801.    

19. König R, Huang LY, Germain RN (1992) MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8. Nature 356: 796–798.    

20. Zhou W, König R (2003) T cell receptor-independent CD4 signalling: CD4-MHC class II interactions regulate intracellular calcium and cyclic AMP. Cell Signal 15: 751–762.    

21. De M, Domingos O, Lewis DJ, et al. (2008) A new oil-based antigen delivery formulation for both oral and parenteral vaccination. Open Drug Deliv J 2: 52–60.    

22. Taylor PR, Koski GK, Paustian CC, et al. (2010) J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells. Vaccine 28: 5533–5542.    

23. Den HJMM, Lehar SM, Bevan MJ (2000) CD8+ but Not CD8− dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192: 1685–1695.    

24. Taylor PR, Paustian CC, Koski GK, et al. (2010) Maturation of dendritic cell precursors into IL12-producing DCs by J-LEAPS immunogens. Cell Immunol 262: 1–5.    

25. Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17: 138–146.    

26. Palucka K, Banchereau J (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39: 38–48.    

27. Vacaflores A, Freedman SN, Chapman NM, et al. (2017) Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production. Mol Immunol 81: 1–15.    

28. Tugues S, Burkhard SH, Ohs I, et al. (2015) New insights into IL-12-mediated tumor suppression. Cell Death Differ 22: 237–246.    

29. Koski GK, Koldovsky U, Xu S, et al. (2012) A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother 35: 54–65.    

30. Boggio K, Di CES, Cavallo F, et al. (2000) Ability of systemic interleukin-12 to hamper progressive stages of mammary carcinogenesis in HER2/neu transgenic mice. Cancer Res 60: 359–364.

31. Hung MC, Lau YK (1999) Basic science of HER-2/neu: a review. Semin Oncol 26: 51–59.

32. Nava-Parada P, Forni G, Knutson KL, et al. (2007) Peptide vaccine given with a toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumors. Cancer Res 67: 1326–1334.    

33. Baxevanis CN, Sotiriadou NN, Gritzapis AD, et al. (2006) Immunogenic HER-2/neu peptides as tumor vaccines. Cancer Immunol Immun 55: 85–95.    

34. Boggio K, Nicoletti G, Carlo ED, et al. (1998) Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. J Exp Med 188: 589–596.    

35. Lowenfeld L, Mick R, Datta J, et al. (2017) Dendritic cell vaccination enhances immune responses and induces regression of HER2pos DCIS independent of route: results of randomized selection design trial. Clin Cancer Res 23: 2961–2971.    

36. Datta J, Terhune JH, Lowenfeld L, et al. (2014) Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med 87: 491–518.

37. Kantoff PW, Higano CS, Shore ND, et al. (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New Engl J Med 363: 411–422.    

38. Fragoulis GE, Siebert S, Mcinnes IB (2016) Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med 67: 337–353.    

39. Amadiobi A, Yu CR, Liu X, et al. (2007) Th17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13: 711–718.    

40. Trinchieri G (2007) Interleukin-10 production by effector T cells: Th1 cells show self control. J Exp Med 204: 239–243.    

Copyright Info: © 2017, Ken S. Rosenthal, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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