NIH starts clinical trial of H5N1 DNA vaccine

Robert Roos

Jan 4, 2007 (CIDRAP News) – Federal officials have announced the launch of the first clinical trial of an H5N1 avian influenza vaccine made from a piece of the virus's DNA rather than from the whole virus, an approach that may facilitate faster vaccine production.

The trial began Dec 21 at the National Institutes of Health (NIH) Clinical Center in Bethesda, Md., the NIH reported in a news release yesterday. The vaccine was designed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH.

Conventional flu vaccines use viruses that are grown in chicken eggs and administered in weakened or killed form, the NIH noted. DNA vaccines, in contrast, contain only parts of the virus's genetic material. "Once inside the body, the DNA instructs human cells to make proteins that act as a vaccine against the virus," the agency said.

The experimental vaccine uses a modified version of the hemagglutinin gene from a recent strain of the deadly H5N1 virus, the NIH reported. It was made in the Vaccine Pilot Plant at the NIAID's Vaccine Research Center (VRC).

VRC Director Gary Nabel, MD, PhD, said the vaccine uses DNA from a 2005 strain of H5N1 from Indonesia. The vaccine is produced by growing bacteria that have been engineered to make the viral DNA, he told CIDRAP News.

The NIH said the DNA vaccine was brought "from the research bench into clinical trials in less than 6 months."

The trial will involve 45 volunteers between the ages of 18 and 60. Thirty volunteers will receive three vaccine injections over 2 months and will be followed for a year, while 15 will receive placebo injections.

Researchers will measure the volunteers' immune response to the vaccine, compare its potency with that of more traditional vaccines, and assess its safety, the NIH said.

Nabel said the new technique has the potential to speed up flu vaccine production, but he stressed that investigators first must show that the vaccine is immunogenic and safe.

He said a batch of the bacteria can be grown in a matter of days, and purification and quality-control steps add a few weeks to the process of making the vaccine. "From start to finish it's probably a couple of months," he said, as compared with about 6 to 8 months for the conventional process of growing the vaccine virus in chicken eggs.

Approximately the same timeline would apply in using the technique to make a vaccine for a new H5N1 strain, according to Nabel. "You can make new prototypes within days, and then it's just a matter of getting it into the fermentation and production process," he said. "Literally it can be just a matter of a couple months to get to a small phase 1 trial."

But he stopped short of suggesting what it would take to scale up production to millions of doses. "Clearly there would be somewhat of a learning curve," he said. "We need to determine whether the DNA vaccine can work and can generate a sufficient amount of the right type of immunity to protect against influenza infections. That's really the purpose of the trial."

If the vaccine performs well in trials and if the H5N1 virus evolves into a pandemic strain within the next couple of years, the vaccine could possibly be of some use in combating it, Nabel said.

He said DNA vaccines generate some level of cellular immune response, whereas traditional flu vaccines generate only a humoral immune (neutralizing antibody) response. When responding to an emerging pandemic virus, for which no precisely matched vaccine would be immediately available, the cellular immunity conferred by a DNA vaccine might be of some help, he said.

Nabel said another possibility is that the DNA vaccine, if it succeeds in clinical trials, could be used in combination with a traditional inactivated vaccine, assuming the traditional vaccine was at least modestly immunogenic. The DNA vaccine could be given first, followed by the traditional vaccine as a booster. (The federal government has a small stockpile of a traditional egg-based vaccine for H5N1, which has generated modest immune responses in trials.)

The DNA vaccine contains no infectious material, and the virus was not present during any part of the manufacturing process, Julie E. Martin, DO, leader of the study, said in the news release.

Nabel and his colleagues have previously shown the efficacy of DNA flu vaccines in lab animals, including animals exposed to H5N1 viruses and the H1N1 virus that caused the 1918 pandemic, the NIH said. The vaccine now being tested is similar to other DNA vaccines in development, including vaccines for HIV, Ebola, SARS (severe acute respiratory syndrome), and West Nile virus.

"Development of this vaccine technology has the potential to improve our production capacity for vaccines to prevent seasonal influenza and other diseases," NIAID Director Anthony S. Fauci, MD, commented in the news release.

Nabel said the NIH vaccine is not the same as the H5N1 DNA vaccine being developed by Vical Inc. of San Diego, though the vaccines are analogous. The NIH has been supporting Vical's research with grants.

Oct 20, 2006, CIDRAP News story "DNA vaccine protects mice from 1918 flu virus"

Jun 7, 2006, CIDRAP News story "Firm gets funds for work on avian flu DNA vaccine"