Reduced Immunogenicity of DNA Vaccine Plasmids in Mixtures

Gene Ther. 2004 Mar;11(5):448-56. doi: 10.1038/sj.gt.3302139.

Abstract

We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-gamma responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-gamma responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-gamma responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / immunology
  • DNA, Protozoan / administration & dosage
  • Dose-Response Relationship, Immunologic
  • Female
  • Immune Tolerance
  • Immunization / methods
  • Interferon-gamma / biosynthesis
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids / immunology
  • Plasmodium falciparum / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Combined / immunology
  • Vaccines, DNA / immunology*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • DNA, Protozoan
  • Malaria Vaccines
  • Vaccines, Combined
  • Vaccines, DNA
  • Interferon-gamma