Skip to main content

Advertisement

You are viewing the new article page. Let us know what you think. Return to old version

Detection of progeny immune responses after intravenous administration of DNA vaccine to pregnant mice

Abstract

A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus) were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work.

References

  1. 1.

    Okuda K, Xin K-Q, Haruki A, Kawamoto S, Kojima Y, Hirahara F, Okada H, Klinman D, Hamajima K. Transplacental genetic immunization after intravenous delivery of plasmid DNA to pregnant mice. J Immunol 2001;167:5478–5484.

  2. 2.

    Spear PG, Edelman GM. Maturation of the humoral immune response in mice. J Exp Med 1974:139:249–263.

  3. 3.

    Billingham RE, Silver WK. Studies on tolerance of the Y chromosome antigen in mice. J Immunol 1960;107:179–202.

  4. 4.

    Burnet FM. The colony selection theory of acquired immunity: Cambridge University Press: Cambridge, England; 1959.

  5. 5.

    Dorsch S, Roser B. T cells mediate transplantation tolerance. Nature 1975;258:233–235.

  6. 6.

    Gammon G, Dunn K, Shastri N, Oki A, Wilbur S, Sercarz EE. Neonatal T-cell tolerance to minimal immunogenic peptides is caused by clonal inactivation. Nature 1986;319:413–415.

  7. 7.

    Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 1998;393:474–478.

  8. 8.

    Ichino M, Mor G, Conover J, Weiss WR, Takeno M, Ishii KJ, Klinman DM. Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine. J Immunol 1999;162:3814–3818.

  9. 9.

    Sarzotti M, Robbins DS, Hoffman PM. Induction of protective CTL responses in newborn mice by a murine retrovirus. Science 1996;271:1726–1728.

  10. 10.

    Tsukamoto M, Ochiya T, Yoshida S, Sugimura T, Terada M. Gene transfer and expression in progeny after intravenous DNA injection into pregnant mice. Nat Genet 1995;9:243–248.

  11. 11.

    Okuda K, Bukawa H, Hamajima K, Kawamoto S, Sekigawa K, Yamada Y, Tanaka S, Ishii N, Aoki I, Nakamura M, Yamamoto H, Cullen BR, Fukushima J. Induction of potent humoral and cell-mediated immune responses following direct injection of DNA encoding the HIV-1 env and rev gene products. AIDS Res Hum Retroviruses 1995;11:933–943.

  12. 12.

    Toda S, Ishii N, Okada E, Kusakabe KI, Arai H, Hamajima K, Gorai I, Nishioka K, Okuda K. HIV-1-specific cell-mediated immune responses induced by DNA vaccination were enhanced by mannan-coated liposomes and inhibited by anti-interferon-γ antibody. Immunology 1997;92:111–117.

  13. 13.

    Cease KB. Peptide component vaccine engineering: targeting the AIDS virus. Int Rev Immunol 1990;7:85–107.

  14. 14.

    Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, Dewitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Petty HC, Shiver JW, Montgomery DL, Liu MA. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 1993;259:1745–1749.

  15. 15.

    Ulmer JB, Deck RR, DeWitt CM, Friedman A, Donnelly JJ, Liu MA. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. Vaccine 1994;12:1541–1544.

  16. 16.

    Ulmer JB, Fu T-M, Deck RR, Friedman A, Guan L, DeWitt C, Liu X, Wang S, Liu MA, Donnelly JJ, Caulfield MJ. Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J Virol 1998;72:5648–5653.

  17. 17.

    el-Naggar AK, van Dekken HD, Ensign LG, Pathak S. Interphase cytogenetics in paraffin-embedded sections from renal cortical neoplasms. Correlation with cytogenetic and flow cytometric DNA ploidy analyses. Cancer Genet Cytogenet 1994;73:134–141.

  18. 18.

    Herr W, Linn B, Leister N, Wandel E, Meyer zum Buschenfelde KH, Wolfel T. The use of computerassisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor alpha spots in response to peptide antigens. J Immunol Methods 1997;203:141–152.

  19. 19.

    Shirai A, Holmes K, Klinman D. Detection and quantitiation of cells secreting IL-16 under physiologic conditions in BALB/c mice. J Immunol 1993;150:793–799.

  20. 20.

    Billingham RE, Brent L, Medawar PB. Activity acquired tolerance of foreign cells. Nature 1953;172:603–605.

  21. 21.

    Mor G, Singla M, Steinberg AD, Hoffman SL, Okuda K, Klinman DM. Do DNA vaccines induce autoimmune disease? Hum Gene Ther 1997;8:293–300.

  22. 22.

    Forsthube T, Yip HC, Lehmann PV. Induction of TH1 and TH2 immunity in neonatal mice. Science 1996;271:1728–1730.

  23. 23.

    Ridge JP, Fuchs EJ, Matzinger P. Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 1996;271:1723–1726.

  24. 24.

    Gerdts V, Babiuk LA, van Drunen Littel-van den Hurk S, Griebel PJ. Fetal immunization by a DNA vaccine delivered into the oral cavity. Nat Med 2000;6:929–932.

Download references

Author information

Correspondence to Ke-Qin Xin or Kenji Okuda.

Additional information

Published: April 23, 2002

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Influenza
  • Influenza Virus
  • Empty Vector
  • Pregnant Mouse
  • Cationic Liposome