The Emerging Role of DNA Vaccines

W. Michael McDonnell, MD, Western Washington Medical Group, and Frederick K. Askari, MD, PhD, University of Michigan.

Disclosures
In This Article

Abstract and Introduction

Abstract

Vaccines composed of DNA are injected into subjects whose own cellular machinery translates the nucleotide sequences into peptides. 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 molecules 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 humans. 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.

Introduction

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

Since 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, the causative agent in hand, foot and mouth disease to Ebola virus.[1,2]

The lack of a vaccine that provides life-long immunity against all strains of influenza virus is a major healthcare problem. A breakthrough came in 1993 with a seminal work in Science demonstrating that a naked DNA vaccine could protect mice against lethal doses of influenza.[3] In addition, investigators also showed the vaccine, based on one strain of influenza, could protect against a different strain.

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