New Vaccines against the Flu
A novel type of vaccine could be rapidly designed for a specific flu strain and then quickly manufactured.
The National Institutes of Health (NIH) recently began a clinical trial of a novel kind of bird-flu vaccine that can be designed and manufactured three times faster than traditional vaccines. These new DNA vaccines, which have shown promise in animals, could help researchers respond rapidly to an emerging flu pandemic.
“The current vaccines for avian flu don’t work well,” says Gary Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, who is leading the DNA vaccine trial. The current vaccines might not even be targeted at the right strain. And while using traditional approaches, a pandemic might claim many lives before a working vaccine can be made: it takes at least six months to design and manufacture a conventional vaccine. DNA vaccines, which simply consist of a gene from a virus or other infectious agent, might help researchers catch up.
Making a conventional influenza vaccine involves predicting which strain of the virus will impact the population, then isolating and purifying it, and growing it in chicken eggs. To make a DNA vaccine, all researchers need is a gene from the virus–they don’t need to grow the virus itself. “DNA vaccines are much more efficient to make,” says Nabel. “You can make new prototypes within days. Production may take another couple months for quality control.”
The NIH vaccine uses a gene from the H5N1 avian-flu virus, the deadly strain that has infected 261 people in Asia. As in all DNA vaccines, the H5N1 gene is carried in a circle of DNA called a plasmid. The plasmids are injected into arm-muscle tissue, whose cells take them up and use the viral gene to make protein–in the case of the NIH vaccine, a protein that appears on the surface of the virus. The protein enters the blood stream, and the immune system, recognizing it as foreign, starts to make antibodies against it. If someone who has been vaccinated with the H5N1 flu gene is infected with the H5N1 virus, the researchers hope these antibodies will help his or her body quickly recognize and fight the infection.
Nabel’s group has demonstrated that a similar DNA vaccine protected mice from infection by both H5N1 and the strain responsible for the 1918 pandemic flu, which killed an estimated 20 to 50 million people worldwide. The NIH trial–the first human test of a bird-flu DNA vaccine–will enroll 45 people and will test the safety of the H5N1 vaccine and whether vaccinated subjects produce enough antibodies to combat infection.
DNA vaccines are also in clinical trials for West Nile virus, Ebola, SARS, and HIV prevention and treatment. Indeed, much of the research done on DNA vaccines in humans has been directed toward developing an HIV vaccine. Nabel says researchers have learned that following a DNA vaccine with a traditional vaccine has a synergistic effect on the immune system’s ability to combat HIV. A phase II clinical trial of such a combined HIV prevention vaccine, sponsored by the vaccine research center, will soon begin recruiting in Africa.
“This is the initial attempt for flu–to find out if we are in the ballpark for protection,” says Nabel. He says that a DNA vaccine alone may be enough to protect the body from flu. If not, the NIH will try a combined approach like those being tested for HIV.
Although Nabel’s is the first DNA vaccine against bird flu to enter clinical trials, San Diego-based Vical is planning to begin clinical testing of a DNA vaccine aimed at another strain of bird flu. Instead of containing genes for a single viral protein, the Vical vaccine has three.
If the bird-flu vaccine is a success, it’s likely that DNA vaccines for seasonal flu would be too. Because flu changes rapidly, a new vaccine must be made annually. Each year, researchers scramble to predict which strain will dominate, then spend six months making the vaccine. And each year, more than 36,000 Americans die of the flu. If researchers could make DNA vaccines, they’d have more time and might be better able to predict which strain they should target, says Margaret Liu, a private consultant and former Merck researcher, who in the mid 1990s was among the first to demonstrate that DNA vaccines can generate a protective immune response in animals.
The holy grail of influenza vaccines, Liu says, is one that would protect against all strains. (See “Universal Flu Vaccines.”) In the interim, DNA vaccines may help researchers meet the biggest challenge: responding rapidly to each year’s new strain, and being prepared to respond quickly to a possible pandemic.
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