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Route and Method of Delivery of DNA Vaccine Influence Immune Responses in Mice and Non-Human Primates

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Abstract

Background

In spite of the large number of studies that have evaluated DNA-based immunization, few have directly compared the immune responses generated by different routes of immunization, particularly in non-human primates. Here we examine the ability of a hepatitis B surface antigen (HBsAg)-encoding plasmid to induce immune responses in mice and non-human primates (rhesus monkeys: Macaca mulatta) after delivery by a number of routes.

Materials and Methods

Eight different injected [intraperitoneal (IP), intradermal (ID), intravenous (IV), intramuscular (IM), intraperineal (IPER), subcutaneous (SC), sublingual (SL), vaginal wall (VW)] and six non-injected [intranasal inhalation (INH), intranasal instillation (INS), intrarectal (IR), intravaginal (IVAG), ocular (Oc), oral feeding (oral)] routes and the gene gun (GG) were used to deliver HBsAg-expressing plasmid DNA to BALB/c mice. Sera were assessed for HBsAg-specific antibodies (anti-HBs, IgG, IgG1, IgG2a) and cytotoxic T lymphocyte (CTL) activity measured. Three of the most commonly used routes (IM, ID, GG) were compared in rhesus monkeys, also using HBsAg-expressing vectors. Monkeys were immunized with short (0-, 4- and 8-week) or long (0-, 12- and 24-week) intervals between boosts, and in the case of GG, also with different doses, and their sera were assessed for anti-HBs.

Results

In one study, anti-HBs were detected in plasma of mice treated by five of eight of the injected and none of the six noninjected routes. The highest levels of anti-HBs were induced by IM and IV injections, although significant titers were also obtained with SL and ID. Each of these routes also induced CTL, as did IPER and VW and one noninjected route (INH) that failed to induce antibodies. In a second study, GG (1.6 µg) was compared to ID and IM (100 µg) delivery. Significant titers were obtained by all routes after only one boost, with the highest levels detected by IM. Delivery to the skin by GG induced exclusively IgG1 antibodies (Th2-like) at 4 weeks and only very low IgG2a levels at later times; ID-immunized mice had predominantly IgG1 at 4 weeks and this changed to mixed IgG1/IgG2a over time. Responses with IM injection (in the leg or tongue) were predominantly IgG2a (Th1-like) at all times. IV injection gave mixed IgG1/IgG2a responses. In monkeys, in the first experiment, 1 mg DNA IM or ID at 0, 4, and 8 weeks gave equivalent anti-HB titers and 0.4 µg at the same times by GG induced lower titers. In the second experiment, 1 mg DNA IM or ID, or 3.2 µg by GG, at 0, 12, and 24 weeks, gave anti-HB values in the hierarchy of GG > IM > ID. Furthermore, high titers were retained after a single immunization in mice but fell off over time in the monkeys, even after boost.

Conclusions

Route of administration of plasmid DNA vaccines influences the strength and nature of immune responses in mice and non-human primates. However, the results in mice were not always predictive of those in monkeys and this is likely true for humans as well. Optimal dose and immunization schedule will most likely vary between species. It is not clear whether results in non-human primates will be predictive of results in humans, thus additional studies are required.

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References

  1. Donnelly JJ, Ulmer JB, Shiver JW, Liu MA. (1997) DNA vaccines. Annu. Rev. Immunol. 15: 617–648.

    Article  CAS  PubMed  Google Scholar 

  2. Davis HL, McCluskie MJ. (1999) DNA vaccines for viral diseases. Microbes and Infection 1: 7–23.

    Article  CAS  PubMed  Google Scholar 

  3. MacGregor RR, Boyer JD, Ugen KE, et al. (1998) First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J. Infect. Dis. 178: 92–100.

    Article  CAS  PubMed  Google Scholar 

  4. Calarota S, Bratt G, Nordlund S, et al. (1998) Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients. Lancet 351: 1320–1325.

    Article  CAS  PubMed  Google Scholar 

  5. Wang R, Doolan DL, Le TP, et al. (1998) Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science 282: 476–480.

    Article  CAS  PubMed  Google Scholar 

  6. Ugen KE, Nyland SB, Boyer JD, et al. (1998) DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans. Vaccine 16: 1818–1821.

    Article  CAS  PubMed  Google Scholar 

  7. Davis HL, Brazolot Millan CL, Watkins SC. (1997) Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA. Gene Ther. 4: 181–188.

    Article  CAS  PubMed  Google Scholar 

  8. Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA. (1997) Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp. Med. 186: 1481–1486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD Jr. (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2: 1122–1128.

    Article  CAS  PubMed  Google Scholar 

  10. Krieg AM, Yi AK, Matson S, et al. (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374: 546–549.

    Article  CAS  PubMed  Google Scholar 

  11. Sato Y, Roman M, Tighe H, et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273: 352–354.

    Article  CAS  PubMed  Google Scholar 

  12. Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL. (1993) DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. U.S.A. 90: 11478–11482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Feltquate DM, Heaney S, Webster RG, Robinson HL. (1997) Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158: 2278–2284.

    PubMed  CAS  Google Scholar 

  14. Pertmer TM, Roberts TR, Haynes JR. (1996) Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery. J. Virol. 70: 6119–6125.

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Davis HL, Whalen RG, Demeneix BA. (1993) Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum. Gene Ther. 4: 151–159.

    Article  PubMed  Google Scholar 

  16. Davis HL, Michel ML, Whalen RG. (1993) DNA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody. Hum. Mol. Genet. 2: 1847–1851.

    Article  CAS  PubMed  Google Scholar 

  17. Davis HL, McCluskie MJ, Gerin JL, Purcell RH. (1996) DNA vaccine for hepatitis B: evidence for immunogenicity in chimpanzees and comparison with other vaccines. Proc. Natl. Acad. Sci. U.S.A. 93: 7213–7218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Davis HL, Schleef M, Moritz P, Mancini M, Schorr J, Whalen RG. (1996) Comparison of plasmid DNA preparation methods for direct gene transfer and genetic immunization. Biotechniques 21: 92–94, 96–99.

    Google Scholar 

  19. Davis HL, Mancini M, Michel ML, Whalen RG. (1996) DNA-mediated immunization to hepatitis B surface antigen: longevity of primary response and effect of boost. Vaccine 14: 910–915.

    Article  CAS  PubMed  Google Scholar 

  20. Cardoso AI, Sixt N, Vallier A, Fayolle J, Buckland R, Wild TF. (1998) Measles virus DNA vaccination: antibody isotype is determined by the method of immunization and by the nature of both the antigen and the coimmunized antigen. J. Virol. 72: 2516–2518.

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Tang D, De Vit M, Johnston SA. (1992) Genetic immunization is a simple method for eliciting an immune response. Nature 356: 152–154.

    Article  CAS  PubMed  Google Scholar 

  22. Raz E, Carson DA, Parker SE, et al. (1994) Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. U.S.A. 91: 9519–9523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gramzinski RA, Brazolot Millan CL, Obaldia N, Hoffman SL, Davis HL. (1998) Immune response to a hepatitis B DNA vaccine in Aotus monkeys—a comparison of vaccine formulation, route, and method of administration. Mol. Med. 4: 109–118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ishii N, Fukushima J, Kaneko T, et al. (1997) Cationic liposomes are a strong adjuvant for a DNA vaccine of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses 13: 1421–1428.

    Article  CAS  PubMed  Google Scholar 

  25. Yokoyama M, Zhang J, Whitton J. (1996) DNA immunization: effects of vehicle and route of administration on the induction of protective antiviral immunity. FEMS Immunol. Med. Microbiol. 14: 221–230.

    Article  CAS  PubMed  Google Scholar 

  26. Liu Y, Mounkes LC, Liggitt HD, et al. (1997) Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery. Nat. Biotech. 15: 167–173.

    Article  CAS  Google Scholar 

  27. Kuklin N, Daheshia M, Karem K, Manickan E, Rouse BT. (1997) Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization. J. Virol. 71: 3138–3145.

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Sasaki S, Hamajima K, Fukushima J, et al. (1998) Comparison of intranasal and intramuscular immunization against human immunodeficiency virus type 1 with a DNA-monophosphoryl lipid A adjuvant vaccine. Infect. Immun. 66: 823–826.

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Okada E, Sasaki S, Ishii N, et al. (1997) Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J. Immunol. 159: 3638–3647.

    PubMed  CAS  Google Scholar 

  30. Chen SC, Jones DH, Fynan EF, et al. (1998) Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. J. Virol. 72: 5757–5761.

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Jones DH, Corris S, McDonald S, Clegg JC, Farrar GH. (1997) Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. Vaccine 15: 814–817.

    Article  CAS  PubMed  Google Scholar 

  32. Etchart NR, Buckland R, Liu MA, Wild TF, Kaiserlian D. (1997) Class I-restricted CTL induction by mucosal immunization with naked DNA encoding measles virus haemagglutinin. J. Gen. Virol. 78: 1577–1580.

    Article  CAS  PubMed  Google Scholar 

  33. Hinkula J, Lundholm P, Wahren B. (1997) Nucleic acid vaccination with HIV regulatory genes: a combination of HIV-1 genes in separate plasmids induces strong immune responses. Vaccine 15: 874–878.

    Article  CAS  PubMed  Google Scholar 

  34. Livingston JB, Lu S, Robinson H, Anderson DJ. (1998) Immunization of the female genital tract with a DNA-based vaccine. Infect. Immun. 66: 322–329.

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Macklin MD, McCabe D, McGregor MW, et al. (1998) Immunization of pigs with a particle-mediated DNA vaccine to influenza A virus protects against challenge with homologous virus. J. Virol. 72: 1491–1496.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Keller ET, Burkholder JK, Shi F, et al. (1996) In vivo particle-mediated cytokine gene transfer into canine oral mucosa and epidermis. Cancer Gene Ther. 3: 186–191.

    PubMed  CAS  Google Scholar 

  37. Wang B, Dang K, Agadjanyan MG, et al. (1997) Mucosal immunization with a DNA vaccine induces immune responses against HIV-1 at a mucosal site. Vaccine 15: 821–825.

    Article  CAS  PubMed  Google Scholar 

  38. Bagarazzi ML, Boyer JD, Javadian MA, et al. (1997) Safety and immunogenicity of intramuscular and intravaginal delivery of HIV-1 DNA constructs to infant chimpanzees. J. Med. Primatol. 26: 27–33.

    Article  CAS  PubMed  Google Scholar 

  39. Daheshia M, Kuklin N, Manickan E, Chun S, Rouse BT. (1998) Immune induction and modulation by topical ocular administration of plasmid DNA encoding antigens and cytokines. Vaccine 16: 1103–1110.

    Article  CAS  PubMed  Google Scholar 

  40. Michel ML, Davis HL, Schleef M, Mancini M, Tiollais P, Whalen RG. (1995) DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans. Proc. Natl Acad. Sci. U.S.A. 92: 5307–5311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Anonymous. (1997) Vectors for gene therapy. In: Dracopoli N, Haines JL, Korf BR, et al. (eds). Current Protocols in Human Genetics. John Wiley and Sons, New York, pp. 12.6.1–12.6.2.

  42. Davis HL, Michel M-L, Mancini M, Schleef M, Whalen RG. (1994) Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 12: 1503–1509.

    Article  CAS  PubMed  Google Scholar 

  43. Davis HL, Weeranta R, Waldschmidt TJ, Tygrett L, Schorr J, Krieg AM. (1998) CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J. Immunol 160: 870–876.

    PubMed  CAS  Google Scholar 

  44. Brazolot Millan CL, Weeratna R, Krieg AM, Siegrist CA, Davis HL. (1998) CpG DNA induces strong Th1 responses against hepatitis B surface antigen in neonatal mice. Proc. Natl. Acad. Sci. U.S.A. 95: 15553–15558.

    Article  CAS  PubMed  Google Scholar 

  45. McCluskie MJ, Davis HL. (1998) CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B surface antigen with intranasal administration to mice. J. Immunol. 161: 4463–4466.

    PubMed  CAS  Google Scholar 

  46. Gregoriadis G, Saffie R, de Souza JB. (1997) Liposome-mediated DNA vaccination. FEBS Lett. 402: 107–110.

    Article  CAS  PubMed  Google Scholar 

  47. Blessing T, Remy JS, Behr JP. (1998) Monomolecular collapse of plasmid DNA into stable viruslike particles. Proc. Natl. Acad. Sci. U.S.A. 95: 1427–1431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Haynes JR, McCabe DE, Swain WF, Widera G, Fuller JT. (1996) Particle-mediated nucleic acid immunization. J. Biotechnol. 44: 37–42.

    Article  CAS  PubMed  Google Scholar 

  49. Krieg AM, Wu T, Weeratna R, et al. (1998) Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc. Natl. Acad. Sci. U.S.A. 95: 12631–12636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Iwasaki A, Stiernholm BJ, Chan AK, Berinstein NL, Barber BH. (1997) Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines. J. Immunol. 158: 4591–4601.

    PubMed  CAS  Google Scholar 

  51. Geissler MA, Gesien A, Tokushige K, Wands JR. (1997) Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids. J. Immunol. 158: 1231–1237.

    PubMed  CAS  Google Scholar 

  52. Fuller DH, Corb MM, Barnett S, Steimer K, Haynes JR. (1997) Enhancement of immunodeficiency virus-specific immune responses in DNA-immunized rhesus macaques. Vaccine 15: 924–926.

    Article  CAS  PubMed  Google Scholar 

  53. Prayaga SK, Ford MJ, Haynes JR. (1997) Manipulation of HIV-1 gp120-specific immune responses elicited via gene gun-based DNA immunization. Vaccine 15: 1349–1352.

    Article  CAS  PubMed  Google Scholar 

  54. Schneider J, Gilbert SC, Blanchard TJ, et al. (1998) Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat. Med. 4: 397–402.

    Article  CAS  PubMed  Google Scholar 

  55. Richmond JFL, Lu S, Santoro JC, et al. (1998) Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 env antibody elicited by DNA priming and protein boosting. J. Virol. 72: 9092–9100.

    PubMed  PubMed Central  CAS  Google Scholar 

  56. Robinson HL, Boyle CA, Feltquate DM, Morin MJ, Santoro JC, Webster RG. (1997) DNA immunization for influenza virus: studies using hemagglutinin- and nucleoprotein-expressing DNAs. J. Infect. Dis. 176: S50–S55.

    Article  CAS  PubMed  Google Scholar 

  57. Robinson HL, Torres CA. (1997) DNA vaccines. Semin. Immunol. 9: 271–283.

    Article  CAS  PubMed  Google Scholar 

  58. Wolff JA, Malone RW, Williams P, et al. (1990) Direct gene transfer into mouse muscle in vivo. Science 247: 1465–1468.

    Article  CAS  PubMed  Google Scholar 

  59. Wolff JA, Ludtke JJ, Acsadi G, Williams P, Jani A. (1992) Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1: 363–369.

    Article  CAS  PubMed  Google Scholar 

  60. Ulmer JB, Deck RR, Dewitt CM, et al. (1996) Expression of a viral protein in muscle cells in vivo induces protective cell-mediated immunity. Immunology 89: 59–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Corr M, Lee DJ, Carson DA, Tighe H. (1996) Gene vaccination with naked plasmid DNA: mechanism of CTL priming. J. Exp. Med. 184: 1555–1560.

    Article  CAS  PubMed  Google Scholar 

  62. Doe B, Selby M, Barnett S, Baenziger J, Walker CM. (1996) Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. Proc. Natl. Acad. Sci. U.S.A. 93: 8578–8583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Iwasaki A, Torres CA, Ohashi PS, Robinson HL, Barber BH. (1997) The dominant role of bone marrow-derived cells in CTL induction following plasmid DNA immunization at different sites. J. Immunol. 159: 11–14.

    PubMed  CAS  Google Scholar 

  64. Torres CA, Iwasaki A, Barber BH, Robinson HL. (1997) Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol. 158: 4529–4532.

    PubMed  CAS  Google Scholar 

  65. Chattergoon MA, Robinson TM, Boyer JD, Weiner DB. (1998) Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells. J. Immunol. 160: 5707–5718.

    PubMed  CAS  Google Scholar 

  66. Mathiowitz E, Jacob JS, Jong YS, et al. (1997) Biologically erodable microspheres as potential oral drug delivery systems. Nature 386: 410–414.

    Article  CAS  PubMed  Google Scholar 

  67. Barry MA, Johnston SA. (1997) Biological features of genetic immunization. Vaccine 15: 788–791.

    Article  CAS  PubMed  Google Scholar 

  68. Cardoso AI, Blixenkrone-Moller M, Fayolle J, Liu M, Buckland R, Wild TF. (1996) Immunization with plasmid DNA encoding for the measles virus hemagglutinin and nucleoprotein leads to humoral and cell-mediated immunity. Virology 225: 293–299.

    Article  CAS  PubMed  Google Scholar 

  69. Boyle JS, Koniaras C, Lew AM. (1997) Influence of cellular location of expressed antigen on the efficacy of DNA vaccination: cytotoxic T lymphocyte and antibody responses are suboptimal when antigen is cytoplasmic after intramuscular DNA immunization. Int. Immunol. 9: 1897–1906.

    Article  CAS  PubMed  Google Scholar 

  70. Mor G, Klinman DM, Shapiro S, et al. (1995) Complexity of the cytokine and antibody response elicited by immunizing mice with Plasmodium yoelii circumsporozoite protein plasmid DNA. J. Immunol. 155: 2039–2046.

    PubMed  CAS  Google Scholar 

  71. Fuller DH, Haynes JR. (1994) A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. AIDS Res. Hum. Retroviruses 10: 1433–1441.

    Article  CAS  PubMed  Google Scholar 

  72. Klinman DM, Yamshchikov G, Ishigatsubo Y. (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158: 3635–3639.

    PubMed  CAS  Google Scholar 

  73. Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. (1997) CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J. Exp. Med. 186: 1623–1631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kim JJ, Ayyavoo V, Bagarazzi ML, et al. (1997) In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. J. Immunol. 158: 816–826.

    PubMed  CAS  Google Scholar 

  75. Kim JJ, Trivedi NN, Nottingham LK, et al. (1998) Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur. J. Immunol. 28: 1089–1103.

    Article  CAS  PubMed  Google Scholar 

  76. Manickan E, Rouse RJ, Yu Z, Wire WS, Rouse BT. (1995) Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes. J. Immunol. 155: 259–265.

    PubMed  CAS  Google Scholar 

  77. Leclerc C, Deriaud E, Rojas M, Whalen RG. (1997) The preferential induction of a Th1 immune response by DNA-based immunization is mediated by the immunostimulatory effect of plasmid DNA. Cell Immunol. 179: 97–106.

    Article  CAS  PubMed  Google Scholar 

  78. Fuller DH, Murphey-Corb M, Clements J, Barnett S, Haynes JR. (1996) Induction of immunodeficiency virus-specific immune responses in rhesus monkeys following gene gun-mediated DNA vaccination. J. Med. Primatol. 25: 236–241.

    Article  CAS  PubMed  Google Scholar 

  79. Wang R, Doolan DL, Charoenvit Y, et al. (1998) Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids. Infect. Immun. 66: 4193–4202.

    PubMed  PubMed Central  CAS  Google Scholar 

  80. Le Borgne S, Mancini M, Le Grand R, et al. (1998) In vivo induction of specific cytotoxic T lymphocytes in mice and rhesus macaques immunized with DNA vector encoding an HIV epitope fused with hepatitis B surface antigen. Virology 240: 304–315.

    Article  PubMed  Google Scholar 

  81. Boyer JD, Wang B, Ugen KE, et al. (1996) In vivo protective anti-HIV immune responses in non-human primates through DNA immunization. J. Med. Primatol. 25: 242–250.

    Article  CAS  PubMed  Google Scholar 

  82. Boyer JD, Ugen KE, Wang B, et al. (1997) Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Nat. Med. 3: 526–532.

    Article  CAS  PubMed  Google Scholar 

  83. Prince AM, Whalen R, Brotman B. (1997) Successful nucleic acid based immunization of newborn chimpanzees against hepatitis B virus. Vaccine 15: 916–919.

    Article  CAS  PubMed  Google Scholar 

  84. Ugen KE, Boyer JD, Wang B, et al. (1997) Nucleic acid immunization of chimpanzees as a prophylactic/immunotherapeutic vaccination model for HIV-1: prelude to a clinical trial. Vaccine 15: 927–930.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Lorraine St. Vincent-Hamblin, Lu Zhang, Lacrimioara Comanita, and Amanda Boyd of the Loeb Health Research Institute for excellent technical assistance. We also thank Max Shapiro of Bioqual, Inc., and Kelledy Manson of Primedica for their valuable assistance. We also thank Dr. Francis Chisari and Patty Fowler, The Scripps Research Institute, La Jolla, CA, for assistance with mouse CTL assays. This research was supported by operating grants from WHO Global Programme for Vaccines and Immunization and MRC (Canada) to H. L. D., who is also a recipient of a Career Scientist Award from the Ontario Ministry of Health. M. J. M. is a recipient of an Ontario Graduate Scholarship from the Ontario Ministry of Education and Training. Studies in rhesus monkeys at Bioqual, Inc., were supported by NIH grant NO1-AI-52705, and those at Primedica were supported by Powder-Ject, Inc.

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Author notes

  1. Georg Widera

    Present address: Gentronics Inc., San Diego, CA, USA

  2. Joel R. Haynes

    Present address: Heska Corporation, 1825 Sharp Point Dr., Ft. Collins, CO, 80525, USA

  3. Harriet L. Robinson

    Present address: Yerkes Research Center, Emory University, Atlanta, GA, 30322, USA

Authors and Affiliations

  1. Loeb Health Research Institute at the Ottawa Hospital, 725 Parkdale Avenue, Ottawa, K1Y 4E9, Canada

    Michael J. McCluskie, Cynthia L. Brazolot Millan &  Heather L. Davis

  2. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada

    Michael J. McCluskie &  Heather L. Davis

  3. Malaria Program, Naval Medical Research Institute, Rockville, Maryland, USA

    Robert A. Gramzinski

  4. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Harriet L. Robinson & Joseph C. Santoro

  5. PowderJect Vaccines, Madison, Wisconsin, USA

    James T. Fuller, Georg Widera & Joel R. Haynes

  6. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Robert H. Purcell

  7. Department of Microbiology, Immunology and Biochemistry, Faculty of Medicine, University of Ottawa, Ottawa, Canada

    Heather L. Davis

  8. School of Rehabilitation Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada

    Heather L. Davis

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McCluskie, M.J., Millan, C.L.B., Gramzinski, R.A. et al. Route and Method of Delivery of DNA Vaccine Influence Immune Responses in Mice and Non-Human Primates. Mol Med 5, 287–300 (1999). https://doi.org/10.1007/BF03402065

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