Modulating the immune response to genetic immunization

Abstract

Genetic immunization, also known as DNA or polynucleotide immunization, is a novel strategy for vaccine development in which plasmid DNA encoding either individual or a collection of antigens is directly administered to a host. Such immunization leads to host expression of the delivered foreign gene, resulting in the induction of a specific immune response against the in vivo produced antigen. DNA immunization has been shown to induce protective immune responses in several infectious disease and cancer experimental model systems. Furthermore, DNA vaccines have recently entered the clinic for analysis as both prophylactic and therapeutic agents. Although the mechanisms of immunity to DNA have not yet been fully elucidated, it has become apparent that the immune response achieved by DNA vaccination is quite malleable, and can be manipulated by altering the conditions under which the vaccine is administered. Either through changing the method or location of immunization, altering the number of immunostimulatory sequences in the plasmid, altering the immunization regimen, or coadministering genes for cytokines or costimulatory molecules, one can modulate both the magnitude and orientation of the subsequent immune response. Through maximization of this feature of DNA immunization, we will likely be able to design vaccines and immunotherapeutic agents that are tailored to the correlates of protection for a particular disease, resulting in a new generation of more focused and effective immune stimulating agents.

Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs

“…DNA-based vaccines can be prepared inexpensively and rapidly on a large scale. Furthermore, the CpG motif in plasmid DNA may cause simultaneous maturation of immature dendritic cells (DCs) and activation of mature DCs 27 and thus can preferentially induce the T helper 1 response, 28 which is important for the antitumor effect.…”

Suppression of Immune Response and Protective Immunity to a Japanese Encephalitis Virus DNA Vaccine by Coadministration of an IL-12-Expressing Plasmid

“…To seek an approach to increase the efficacy of the pE DNA vaccine, we tested the use of cytokines as immunological adjuvants. It has been previously demonstrated that the magnitude and nature of the immune responses to DNA vaccines can be regulated by coadministration of a broad panel of cytokine genes (25)(26)(27). Among these cytokine genes, the IL-12 gene promotes Th1 responses and cell-mediated immunity, and the IL-4 gene favors Th2 cell development and production of Abs.…”

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system

“…6 While peptide, protein or glycoprotein vaccines elicit mainly antibody responses, DNA vaccines allow presentation of antigen to the immune system in several ways and have the potential of inducing strong cellular responses. DNA vaccines have been shown to stimulate all three arms of the immune system, that is, antibody, helper T, and cytotoxic T-cell (CTL) responses, 16 to produce immunity in several disease models such as influenza, 17,18 HIV-1, 19,20 and hepatitis B, 21 and to protect animals from subsequent challenge. 18 The mechanisms are considered to involve antigen presentation by both myocytes and antigen-presenting cells (APCs), as well as crosspriming between the two MHC paths.…”