Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1075210.32607/20758251-2010-2-1-53-59ArticlesСтатьиReview ArticleRegulation of immunogen processing: signal sequences and their application for the new generation of DNA-vaccinesRegulation of immunogen processing: signal sequences and their application for the new generation of DNA-vaccinesStarodubovaE Sestarodubova@yandex.ruIsaguliantsM Gmaria.isaguliants@smi.seKarpovV LEngelhardt Institute of Molecular Biology, Russian Academy of ScienceKarolinska InstitutetIvanovsky Institute of Virology, Russian Academy of Medical ScienceEngelhardt Institute of Molecular Biology, Russian Academy of Science1503201021VOL 2, NO1 (2010)ТОМ 2, №1 (2010)535917012020Copyright ©; 2010, Starodubova E.S., Isaguliants M.G., Karpov V.L.Copyright ©; 2010, Starodubova E.S., Isaguliants M.G., Karpov V.L.2010Starodubova E.S., Isaguliants M.G., Karpov V.L.Starodubova E.S., Isaguliants M.G., Karpov V.L.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10752

Immunization with naked genes (DNA-immunization) is a perspective modern approach to prophylactic as well as therapeutic vaccination against pathogens, as well as cancer and allergy. A panel of DNA immunogens has been developed, some are already in the clinical trials. However, the immunogenicity of DNA vaccines, specifically of those applied to humans, needs a considerable improvement. There are several approaches to increase DNA vaccine immunogenicity. One approach implies the modifications of the encoded immunogen that change its processing and presentation, and thus the overall pattern of anti-immunogen response. For this, eukaryotic expression vectors are constructed that encode the chimeric proteins composed of the immunogen and specialized targeting or signal sequences. The review describes a number of signals that if fused to immunogen, target it into the predefined subcellular compartments. The review gives examples of their application for DNA-immunization.

DNA -vaccinesMHC-IIantigen presentationМНС-INichols W.W., Ledwith B.J., Manam S.V., et al. // Ann N Y Acad Sci. 1995. V. 772. P. 30-39.Powell K. // Nat. Biotechnol. 2004. V. 22. P. 799-801.Breathnach C.C., Clark H.J., Clark R.C., et al. // Vaccine. 2006. V. 24. P. 1180-1190.Bahloul C., Taieb D., Diouani M.F., et al. // Vaccine. 2006. V. 24. P. 1063-1072.Liu M.A., Wahren B. and Karlsson Hedestam G.B. // Hum. Gene Ther. 2006. V. 17. P. 1051-1061.Ulmer J.B., Wahren B. and Liu M.A. // Trends Mol. Med. 2006. V. 12. P. 216-222.Ahlen G., Soderholm J., Tjelle T., et al. // J. Immunol. 2007. V. 179. P. 4741-4753.Cui Z. // Adv. Genet. 2005. V. 54. P. 257-289.Laddy D.J. and Weiner D.B. // Int. Rev. Immunol. 2006. V. 25. P. 99-123.Duerr A., Wasserheit J.N. and Corey L. // Clin. Infect. Dis. 2006. V. 43. P. 500-511.Donnelly J.J., Wahren B. and Liu M.A. // J. Immunol. 2005. V. 175. P. 633-639.Kutzler M.A. and Weiner D.B. // Nat. Rev. Genet. 2008. V. 9. P. 776-788.Barouch D.H. // J. Pathol. 2006. V. 208. P. 283-289.Jechlinger W. // Expert Rev. Vaccines. 2006. V. 5. P. 803-825.Egan M.A., Megati S., Roopchand V., et al. // Vaccine. 2006. V. 24. P. 4510-4523.Megati S., Garcia-Hand D., Cappello S., et al. // Vaccine. 2008. V. 26. P. 5083-5094.Leifert J.A., Rodriguez-Carreno M.P., Rodriguez F., et al. // Immunol. Rev. 2004. V. 199. P. 40-53.Yewdell J.W. // Curr. Opin. Immunol. 2007. V. 19. Р. 79-86.van Bergen J., Ossendorp F., Jordens R., et al. // Immunol. Rev. 1999. V. 172. Р. 87-96.Hershko A. and Ciechanover A. // Annu. Rev. Biochem. 1998. V. 67. P. 425-479.Bachmair A. and Varshavsky A. // Cell. 1989. V. 56. Р. 1019-1032.Rogers S., Wells R. and Rechsteiner M. // Science. 1986. V. 234. Р. 364-368.Yamano H., Gannon J. and Hunt T. // Embo J. 1996. V. 15. P. 5268-5279.Bonifacino J.S. and Traub L.M. // Annu Rev. Biochem. 2003. V. 72. Р. 395-447.Restifo N.P., Bacik I., Irvine K.R., Yewdell J.W., McCabe B.J., Anderson R.W., Eisenlohr L.C., Rosenberg S.A., Bennink J.R. // J. Immunol. 1995. V. 154. P. 4412-4422.Townsend A., Bastin J., Gould K., Brownlee G., Andrew M., Coupar B., Boyle D., Chan S., Smith G. // J. Exp. Med. 1988. V. 168. Р. 1211-1224.Wong S.B.J., Buck C.B., Shen X., Siliciano R.F. // J. Immunology. 2004. V. 173. P 3073-3083.Wu Y., Kipps T.J. // J. Immunol. 1997. V. 159. Р. 6037-6043.Tobery T. and Siliciano R.F. // J. Immunol. 1999. V. 162. P. 639-642.Singh R.A., Wu L. and Barry M.A. // J. Immunol. 2002. V. 168. P. 379-391.Bazhan S.I., Belavin P.A., Seregin S.V., et al. // Vaccine. 2004. V. 22. Р. 1672-1682.Ilyinskii P.O., Meriin A.B., Gabai V.L., et al. // Vaccine. 2008. V. 26. Р. 2177-2185.Altstein A.D., Gitelman A.K., Smirnov Y.A., Piskareva L.M., Zakharova L.G., Pashvykina G.V., Shmarov M.M., Zhirnov O.P., Varich N.P., Ilyinskii P.O., Shneider A.M. // Arch. Virol. 2006. V. 151. P. 921-931.Wong S.B., Buck C.B., Shen X., et al. // J. Immunol. 2004. V. 173. Р. 3073-3083.Vidalin O., Tanaka E., Spengler U., et al. // DNA Cell. Biol. 1999. V. 18. P. 611-621.Orlowski M. and Wilk S. // Arch. Biochem. Biophys. 2003. V. 415. Р. 1-5.Murakami Y., Matsufuji S., Kameji T., et al. // Nature. 1992. V. 360. Р. 597-599.Hayashi S., Murakami Y. and Matsufuji S. // Trends Biochem. Sci. 1996. V. 21. P. 27-30.Murakami Y., Matsufuji S., Hayashi S., et al. // Biochem. Biophys. Res. Commun. 2000. V. 267. Р. 1-6.Starodubova E.S., Boberg A., Litvina M., et al. // Vaccine. 2008. V. 26. P. 5170-5176.Isaguliants M.G., Zuber B., Boberg A., et al. // Vaccine. 2004. V. 22. P. 1810-1819.Boberg A. and Isaguliants M. // Expert Rev. Vaccines. 2008. V. 7. Р. 131-145.Nash P.D., Opas M. and Michalak M. // Mol. Cell. Biochem. 1994. V. 135. Р. 71-78.Spee P. and Neefjes J. // Eur. J. Immunol. 1997. V. 27. Р. 2441-2449.Sadasivan B., Lehner P.J., Ortmann B., et al. // Immunity. 1996. V. 5. P. 103-114.Cheng W.F., Hung C.F., Chai C.Y., et al. // J. Clin. Invest. 2001. V. 108. Р. 669-678.Cheng W.F., Hung C.F., Chen C.A., et al. // Vaccine. 2005. V. 23. Р. 3864-3874.Peng S., Ji H., Trimble C., et al. // J. Virol. 2004. V. 78. Р. 8468-8476.Hung C.F., Hsu K.F., Cheng W.F., et al. // Cancer Res. 2001. V. 61. Р. 1080-1088.Sominskaya I., Alekseeva E., Skrastina D., et al. // Mol. Immunol. 2006. V. 43. P 1941-1952.Klionsky D.J. and Emr S.D. // Science. 2000. V. 290. P. 1717-1721.Yorimitsu T. and Klionsky D.J. // Cell. Death Differ. 2005. V. 12 Suppl. 2. Р. 1542-1552.Paludan C., Schmid D., Landthaler M., et al. // Science. 2005. V. 307. Р. 593-596.Deretic V. // Curr. Opin. Immunol. 2006. V. 18. P. 375-382.Majeski A.E. and Dice J.F. // Int. J. Biochem. Cell. Biol. 2004. V. 36. P. 2435-2444.Prlic M., Williams M.A., Bevan M.J. // Curr. Opin. Immunol. 2007. V. 19. Р. 315-319.Epstein J.E., Gorak E.J., Charoenvit Y., et al. // Hum. Gene. Ther. 2002. V. 13. P. 1551-1560.Bonifacino J.S. and Glick B.S. // Cell. 2004. V. 116. Р. 153-166.Bonifacino J.S. and Dell'Angelica E.C. // J. Cell. Biol. 1999. V. 145. Р. 923-926.Letourneur F. and Klausner R.D. // Cell. 1992. V. 69. Р. 1143-1157.Helenius A. and Aebi M. // Annu. Rev. Biochem. 2004. V. 73. Р. 1019 -1049.Baranski T. J., Faust P.L. and Kornfeld S. // Cell. 1990. V. 63. P. 281-291.Steet R., Lee W.S. and Kornfeld S. // J. Biol. Chem. 2005. V. 280. P. 33318-33323.Munz C. // Cell. Microbiol. 2006. V. 8. P. 891-898.Odorizzi C.G., Trowbridge I.S., Xue L., et al. // J. Cell. Biol. 1994. V. 126. P. 317-330.Gupta S.N., Kloster M.M., Rodionov D.G., et al. // Eur. J. Cell. Biol. 2006. V. 85. P. 457-467.Wu T.C., Guarnieri F.G., Staveley-O'Carroll K.F., et al. // Proc. Natl. Acad. Sci. U S A. 1995. V. 92. Р. 11671-11675.Marques E.T., Jr., Chikhlikar P., de Arruda L.B., et al. // J. Biol. Chem. 2003. V. 278. P. 37926-37936.Ruff A.L., Guarnieri F.G., Staveley-O'Carroll K., et al. // J. Biol. Chem. 1997. V. 272. P. 8671-8678.de Arruda L.B., Chikhlikar P.R., August J.T., et al. // Immunology. 2004. V. 112. P 126-133.Starodubova E., Boberg A., Ivanov A., et al. // Vaccine. 2010. V. 28. P. 1975-1986.Raviprakash K., Marques E., Ewing D., et al. // Virology. 2001. V. 290. P. 74-82.Anwar A., Chandrasekaran A., Ng M.L., et al. // Virology. 2005. V. 332. Р. 66-77.Chen C.H., Wang T.L., Hung C.F., et al. // Vaccine. 2000. V. 18. Р. 2015-2022.Ji H., Wang T.L., Chen C.H., et al. // Hum. Gene. Ther. 1999. V. 10. Р. 2727-2740.Deng H., Kowalczyk D., O.I., et al. // Cell. Immunol. 2002. V. 215. Р. 20-31.Bakke O. and Dobberstein B. // Cell. 1990. V. 63. P. 707-716.Lotteau V., Teyton L., Peleraux A., et al. // Nature. 1990. V. 348. Р. 600-605.Sanderson S., Frauwirth K. and Shastri N. // Proc. Natl. Acad. Sci. USA. 1995. V. 92. Р. 7217-7221.Holst P.J., Sorensen M.R., Mandrup Jensen C.M., et al. // J. Immunol. 2008. V. 180. P 3339-3346.Mwangi W., Brown W.C., Splitter G.A., et al. // Clin. Vaccine Immunol. 2007. V. 14. P. 304-311.Schmid D., Pypaert M. and Munz C. // Immunity. 2007. V. 26. Р. 79-92.Rosati M., von Gegerfelt A., Roth P., et al. // J. Virol. 2005. V. 79. Р. 8480-8492.