Abstract
DNA vaccination with the plasmid expressing Japanese encephalitis virus (JEV) nonstructural protein 1 (pJNS1) has been shown to induce effective immunity against JEV infection. To further increase the efficacy of pJNS1 DNA vaccination, we coinjected pJNS1 with a plasmid that expresses heat shock protein 70.1 (pHSP70.1) into mice. We found that coinjection of pHSP70.1 enhanced both T cell proliferation and cytotoxic effects, but not the antibody response to JEV. Moreover, mice immunized with both pHSP70.1 and pJNS1 were resistant to lethal challenges of JEV, indicating that the protective immunity against JEV is not decreased, in spite of the low antibody titer via the immunization of pHSP70.1. Since DNA vaccination administered by pJNS1 did not elicit strong cellular immunity in our previous study, the administration of pHSP70.1 apparently could be used as an adjuvant to enhance cell-mediated immunity in this model system. Thus, coadministration of pHSP70.1 DNA with plasmid DNA encoding tumor- or virus-specific antigens might be very useful in the treatment of cancers and other infectious diseases.
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Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Ann Rev Microbiol 44:649–688;1990.
Chen LK, Liao CL, Lin CG, Lai SC, Liu CI, Ma SH, Huang YY, Lin YL. Persistence of Japanese encephalitis virus is associated with abnormal expression of nonstructural protein NS1 in host cells. Virology 217:220–229;1996.
Chen LK, Lin YL, Liao CL, Lin CG, Huang YL, Yeh CT, Lai SC, Jan JT, Chin C. Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro. Virology 223:79–88;1996.
Chow YH, Chiang BL, Lee YL, Chi WK, Lin WC, Chen YT, Tao MH. Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J Immunol 160:1320–1329;1998.
Ciupitu AM, Petersson M, O'Donnell CL, Williams K, Jindal S, Kiessling R, Welsh RM. Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes. J Exp Med 187:685–691;1998.
Conry RM, Widera G, LoBuglio AF, Fuller JT, Moore SE, Barlow DL, Turner J, Yang NS, Curiel DT. Selected strategies of augment polynucleotide immunization. Gene Ther 3:67–74;1996.
Cox GJ, Zamb TJ, Babiuk LA. Bovine herpesvirus 1: Immune responses in mice and cattle injected with plasmid DNA. J Virol 67:5664–5667;1993.
Davis HL, Michel ML, Whalen RG. DNA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody. Hum Mol Genet 2:1847–1851;1993.
Donnelly JJ, Friedman A, Martinez D, Montgomery DL, Shiver JW, Motzel SL, Ulmer JB, Liu MA. Preclinical efficacy of a prototype DNA vaccine: Enhanced protection against antigenic drift in influenza virus (see comments). Nat Med 1:583–587;1995.
Gilboa E. The makings of a tumor rejection antigen. Immunity 11:263–270;1999.
Hoke CH, Nisalak A, Sangawhipa N, Jatanasen S, Laorakapongse T, Innis BL, Kotchasenee S, Gingrich JB, Latendresse J, Fukai K, et al. Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med 319:608–614;1988.
Horspool JH, Perrin PJ, Woodcock JB, Cox JH, King CL, June CH, Harlan DM, St. Louis DC, Lee KP. Nucleic acid vaccine-induced immune responses require CD28 costimulation and are regulated by CTLA4. J Immunol 160:2706–2714;1998.
Kim JJ, Bagarazzi ML, Trivedi N, Hu Y, Kazahaya K, Wilson DM, Ciccarelli R, Chattergoon MA, Dang K, Mahalingam S, Chalian AA, Agadjanyan MG, Boyer JD, Wang B, Weiner DB. Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nat Biotechnol 15:641–646;1997.
Ku CC, King CC, Lin CY, Hsu HC, Chen LY, Yueh YY, Chang GJ. Homologous and heterologous neutralization antibody responses after immunization with Japanese encephalitis vaccine among Taiwan children. J Med Virol 44:122–131;1994.
Lin YL, Chen LK, Liao CL, Yeh CT, Ma SH, Chen JL, Huang YL, Chen SS, Chiang HY. DNA immunization with Japanese encephalitis virus nonstructural protein NS1 elicits protective immunity in mice. J Virol 72:191–200;1998.
Major ME, Vitvitski L, Mink MA, Schleef M, Whalen RG, Trepo C, Inchauspe G. DNA-based immunization with chimeric vectors for the induction of immune responses against the hepatitis C virus nucleocapsid. J Virol 69:5798–5805;1995.
Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG. Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4:581–587;1998.
Milner CM, Campbell RD. Structure and expression of the three MHC-linked HSP70 genes. Immunogenetics 32:242–251;1990.
Roman E, Moreno C. Synthetic peptides non-covalently bound to bacterial hsp 70 elicit peptide-specific T-cell responses in vivo. Immunology 88:487–492;1996.
Schirmbeck R, Bohm W, Ando K, Chisari FV, Reimann J. Nucleic acid vaccination primes hepatitis B virus surface antigen-specific cytotoxic T lymphocytes in nonresponder mice. J Virol 69:5929–5934;1995.
Sedegah M, Hedstrom R, Hobart P, Hoffman SL. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci USA 91:9866–9870;1994.
Shiver JW, Perry HC, Davies ME, Freed DC, Liu MA. Cytotoxic T lymphocyte and helper T cell responses following HIV polynucleotide vaccination. Ann NY Acad Sci 772:198–208;1995.
Suzue K, Young RA. Adjuvant-free hsp70 fusion protein system elicits humoral and cellular immune responses to HIV-1 p24. J Immunol 156:873–879;1996.
Tamura Y, Peng P, Liu K, Daou M, Srivastava PK. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278:117–120;1997.
Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein (see comments). Science 259:1745–1749;1993.
Vaughn DW, Hoke CH Jr. The epidemiology of Japanese encephalitis: Prospects for prevention. Epidemiol Rev 14:197–221;1992.
Wang B, Boyer J, Srikantan V, Coney L, Carrano R, Phan C, Merva M, Dang K, Agadjanan M, Gilbert L, et al. DNA inoculation induces neutralizing immune responses against human immunodeficiency virus type 1 in mice and nonhuman primates. DNA Cell Biol 12:799–805;1993.
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL. Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468;1990.
Wolff JA, Williams P, Acsadi G, Jiao S, Jani A, Chong W. Conditions affecting direct gene transfer into rodent muscle in vivo. Biotechniques 11:474–485;1991.
Xiang Z, Ertl HC. Manipulation of the immunre response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2:129–135;1995.
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Chen, WH., Lin, YL., Liao, CL. et al. Modulatory effects of the human heat shock protein 70 on DNA vaccination. J Biomed Sci 7, 412–419 (2000). https://doi.org/10.1007/BF02255816
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DOI: https://doi.org/10.1007/BF02255816