The Emerging Role of DNA Vaccines

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

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In This Article

DNA Vaccine for Influenza

The naked DNA vaccine created at Merck Research Laboratories under the direction of Dr. Margaret Liu against influenza virus uses the nucleoprotein (core) gene of the virus. The nucleoprotein is similar across many strains of influenza, unlike envelope or surface proteins which change extensively form one strain to another. Nucleoproteins are "internal proteins" of the virus and are not subject to the same humoral immune pressure with antigenic drift as are the surface glycoproteins.

In mouse and chicken studies this vaccine has protected the animals against lethal doses of several different strains of influenza; something current vaccines are unable to do. The vaccine has also been shown to induce an immune response and decrease viral shedding in nonhuman primates and ferrets.[9,10] Naked DNA vaccines do induce a humoral immune response in addition to a cell-mediated response but studies have shown that the antibody response alone is not able to protect mice from lethal doses of virus, leading to the conclusion that cell-mediated immunity is necessary for protection.[3]

An immediate question about this vaccine approach is why should it work to stimulate protection against several different strains of influenza virus when even infection with native influenza virus does not. Infection with native influenza virus or live attenuated influenza vaccine should result in cytosolic production of core protein, MHC class I processing, and activation of cytotoxic T lymphocytes (CTLs) -- the same sequence of events effected by a DNA vaccine. Native infection does induce a cell-mediated immunity response but it is not adequate to fight heterologous strains of influenza. Naked DNA vaccines, at least in these animal models, appear to stimulate cell-mediated immunity more efficiently.

How long the immunity induced by DNA vaccines will last is a critical question, but the answer is not known. Investigators report that after one year, immunized mice are still fully protected against a lethal dose of influenza.[3]It is hoped that this technology will lead to a vaccine which confers lifelong immunity against all strains of influenza using just one dose. Human trials sponsored by Merck Inc., are currently underway at Johns Hopkins University to determine the safety and efficacy of the influenza vaccine.

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