Genetic Immunization by Adrian Bot, Constantin A. Bona

By Adrian Bot, Constantin A. Bona

Wolf's discovery demonstrating reporter gene is expressed in myocytes next to injection of bare DNA, used to be exploited by way of immunologists and vaccinologists to increase a brand new new release of vaccines. This remark galvanized the learn and in a brief lapse of time, an oceanic quantity of data has been gathered. The study performed in quite a few animal versions confirmed the efficacy of genetic immunization opposed to viruses, micro organism, and a few parasites via the facility to urge a powerful priming impact because of long-lasting endurance of plasmid as episomes. in addition, it used to be confirmed that baby or youngster immune unresponsiveness to classical vaccines may be corrected via genetic immunization. The purposes of genetic immunization for prophylaxis of infections used to be prolonged to immunotherapy, particularly, cancerous, vehicle┬ş immune, and allergic ailments. Immunologists have supplied pertinent info at the mobile foundation of the immune responses elicited via genetic immunization, and molecular biologists have validated the molecular foundation of intrinsic adjuvant houses of plasmids.

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The role of ISS in adjuvanticity of plasmids was demonstrated in three pioneering experiments. Sato et al. (1996) have studied the immune response against 13-galactosidase elicited by two plasmids expressing Lac Z gene. One plasmid contained kanR gene and the other ampR gene. While ampR gene expresses CpG motifs, the kanR gene did not. Only the animals immunized with plasmid expressing kanR gene were able to induce an immune response. Inability of the plasmid carrying ampR gene to induce antibody synthesis was restored subsequent to coinjection of both plasmids.

However, the ISS have also potentially toxic side-effect properties. , 1997a). , 1996) and induces a dose-dependent splenomegaly. , 2000). 2 illustrates the strong inflammatory reaction at the site of injection of a plasmid or CpG ODN in BALB/c or BALB/c IFN'Y-1- mice. This reaction, also a doubleedged sword, by stimulation of secretions of IFN'Y may not only upregulate the expression of MHC antigens on APC, but can also promote immunomediated processes leading to tissue damage. 7. MECHANISMS OF LYMPHOCYTE ACTIVATION BY CpG ODN The mechanisms of action of CpG ODN are not completely unraveled yet.

The activation of various genes can be due to increased transcriptional activity of promoters. This is well supported by Yi et al. (1996b), who showed increased IL-6 promoter activity subsequent to incubation with CpG ODN of cells transfected with a vector in which the transcription of CAT reporter gene was driven by human IL-6 promoter. Further studies are required to determine the molecular mechanisms involved in CpG ODN gene activation. 1. INTRODUCTION The mechanisms of the induction of immune response by genetic immunization were a mystery during the five-year period when the major effort was focused to determine the immune response induced by plasmids containing genes coding for a variety of antigens.

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