DNA Vaccine: New Advent in Drug Development

Vimal Kumar, Sarvesh Sharma, Mayank Shrivastava, Yaseen Khan

Abstract: Vaccines composed of DNA, when injected into subjects the cellular machinery of subjects translates the nucleotide sequences into peptides which act as antigens. The peptides are presented in the context of MHC class I molecules, and are therefore capable of inducing a brisk cellular immune response, in contrast with traditional vaccines which produce mainly a humoral immune response. DNA may be transferred into the cell by retrovirus, vaccinia virus or adenovirus vectors or by attachment to cationically charged carriers such as liposomes, calcium salts or dendrimers. Alternatively, the desired gene may be directly inserted into a plasmid and the naked DNA simply injected intramuscularly. Naked plasmid DNA vaccines bypass the problem of safety and manufacturing issues arising when viral vectors are used, and also avoid complications or interference from an immune response directed at the delivery vector. For all delivery methods, there is the unproved potential for insertional mutagenesis. There is also the concern of inducing tolerance rather than resistance or anti-DNA antibody formation, leading to autoimmune diseases. There are no DNA vaccines on the market, nor even any published data showing efficacy in Man. Human trials are underway testing the safety and efficacy of DNA vaccines against influenza, malaria, hepatitis B virus, HIV, herpes simplex virus, colon cancer and cutaneous T cell lymphoma. While these early studies have only just begun to provide suggestions of vaccine efficacy, the concepts brought forth by DNA vaccines have dramatically changed the way many investigators in the basic sciences are approaching their work.

A DNA vaccine contains a nucleotide sequence encoding a key antigenic determinant from a given pathogen that is injected into a host, then translated by host cells into a peptide that is foreign to the host. Therefore, the protein is capable of inducing an immune response which confers protection against the given pathogen.

DNA-mediated immunization, colloquially known as DNA vaccines, represents a radical change in the way that antigens are delivered; it involves the direct introduction of a plasmid DNA encoding an antigenic protein which is then expressed within cells of the organism. This leads to surprisingly strong immune responses, involving both the humoral and cellular arms of the immune system. DNA-mediated immunization to a single antigen can provide protection against infection by a pathogen. This approach to immunization will greatly facilitate studies of immunophysiological responses to antigens of pathogenic organisms. After the first report of a DNA vaccine, there has been an explosion of work on numerous pathogens with the hope of introducing a new era of immunization against diseases which have not yielded to conventional vaccine production techniques. Human trials testing the safety and efficacy of vaccines against influenza, malaria, HIV, herpes simplex virus (HSV), colon cancer and cutaneous T cell lymphoma are underway. In addition, animal studies are ongoing for many human pathogens, from coxsackievirus A-16.


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