Simultaneous GeneGun immunisation with plasmids encoding antigen and GM-CSF: significant enhancement of murine antivenom IgG1 titres

GeneGun DNA immunisation is a potent means of inducing antibody-dominant immune responses that we are exploiting to generate venom toxin-specific antibodies to improve the therapy of systemic envenoming by snakes. Here, we report that mice immunised with DNA encoding the carboxyl domain (JD9) of a haemorrhagic Zn metalloprotease (Jararhagin) in venom of the South American pit viper, Bothrops jararaca, and a plasmid expressing murine cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) raised significantly higher antigen-specific IgGl titres than mice immunised with JD9 DNA alone. Serological responses to GeneGun JD9 DNA immunisation were shown to be dominated by IgGl, an IgG subclass associated with T lymphocyte helper 2 (Th2) immune responses. Further significant enhancement of JD9-specific IgGl titres was achieved by increasing the number of immunisations. This report illustrates that DNA immunisation protocols to achieve high-titre, venom toxin-specific antibody production are well advanced and encourage the development of a DNA-based approach to antivenom production. (C) 2002 Elsevier Science Ltd. All rights reserved.