Toward a Universal Flu Vaccine
The first doses of H1N1 flu (swine flu) vaccine are due to be shipped to hospitals around the country in the next few weeks–seven months after the virus strain was first identified. These vaccine doses will use either inactivated or weakened live viruses to prompt immunity–an approach that can fail if any of the live viruses is strong enough to replicate, or if the inactivated viruses have been killed beyond all immune recognition.
One biomed company is working to completely revolutionize how vaccines are produced and applied. As Inovio CEO Joseph Kim will describe at the EmTech@MIT 2009 conference on Wednesday, the group is developing a vaccination that could someday protect against all flu strains simultaneously– including avian and swine flu–in one shot. The first human trials are set to begin next year.
The flu virus manages to temporarily evade our immune systems year after year because it mutates so quickly. To fight off the most virulent strains as they emerge, researchers have to change the vaccine every year. Today, most influenza vaccines are grown in chicken eggs, a process that takes six months or more, and they only protect against a few strains of flu–whichever ones experts believe will be circulating during the next flu season.
Inovio hopes to swap this arduous process for one that involves a DNA-based vaccine. With this approach, small bits of DNA that are found in every human flu virus are engineered to be taken up by cells, thereby prompting the cells to produce antibodies against different strains of viral invaders in order to marshal the appropriate immune response.
“We felt it was time for a change. Having to guess at which strains to protect society against for the coming fall is a very antiquated system, with very small room for error,” says Kim, who is also a 2002 TR35 Young Innovator. “We don’t accept that for any other vaccine protocol. You don’t change the measles-mumps-rubella vaccine every year.”
DNA vaccines can be quickly modified, are cheap to produce, and have a much longer shelf life than traditional vaccines. But they suffer from one large drawback: typical injections result in very little DNA being taken up by cells. Inovio is working on that problem by combining vaccines with a technique called electroporation, which delivers a tiny electric shock right after injection. The shock momentarily disrupts cell membranes and enhances DNA uptake.
To create the DNA vaccines, Inovio uses a platform it calls SynCon–short for “synthetic construct.” Using genetic data and complex algorithms, the company has developed a process for designing consensus genes–synthetic ones that look similar enough to components from a variety of viruses, eliciting an immune response broad enough to fight off different strains of the same disease. Inovio’s system identifies the amino acids that are most often present in each position of a few of the virus’s most important genes, then strings these together to create an antigen that induces immunity to a virus with any of these genes.
“To me, it’s a wonderful advance,” says Tom Edgington, an immunologist and professor emeritus at Scripps Research Institute in San Diego. “With DNA vaccines, there is no issue about having a live particle in there anywhere. You can make very large amounts of DNA and keep it for years, and you don’t have to infect a half-million eggs every year.”
The H in H1N1 stands for hemagglutinin, the virus’s outer protein and one that human immune systems respond to. There are 15 known versions of the protein, only five of which are specific to human disease. So by targeting these hemagglutinin proteins, Inovio’s system should, at least in theory, be effective not just for seasonal flu, but for avian (H5N1) and swine (H1N1) flu as well. “There’s nothing magical about swine H1N1 versus seasonal flu,” Kim says. “It’s just a divergence from what your body has been exposed to, and looks different enough to the immune system to evade it.”
In animal tests, this certainly seems to be the case. The company has tested the H1 component of the vaccine in mice infected with the virulent, epidemic-causing 1918 version of the H1N1 virus. The vaccine prevented any visible symptoms in inoculated mice, while every single one of the nonvaccinated mice died.
Of course, putting something as novel as an electroporation vaccine into widespread use could prove difficult especially because it requires its own technology, which is currently expensive. “If you have to do electroporation, that could potentially be a difficult thing to implement, certainly more difficult than spraying something up someone’s nose,” says Greg Poland, director of the Mayo Clinic’s Vaccine Research Group, in Rochester, MN. (This is how live, weakened-virus flu vaccines are currently administered; inactivated-virus vaccines are given with the classic needle and syringe.)
As far as the vaccine itself goes, most of the experts are in agreement. “The idea is a very good one, the need is a great one, and any company that would make a dent into this would certainly be a winner,” says virologist Peter Palese, head of the microbiology department at Mount Sinai School of Medicine, in New York City. But, although the company’s animal studies are an improvement over earlier DNA vaccination results, he notes that “the proof of the pudding will lie in human trials.”
Inovio has tested its H1 and H5 components in animals, and the group hopes to start human trials of the H5 component in early 2010. H1 tests, they believe, are just a short distance behind. “We think it would likely take two shots, a month apart, and then a booster every five years,” Kim says.
Inovio isn’t limiting itself to influenza, either. It has an HIV vaccine in development and is also working to create vaccines for diseases that are of greater concern in developing countries: malaria and dengue are at the top of the list. In contrast to the $20 billion flu-vaccine market, though, “such vaccines hold promise but will never even start to pay for themselves,” says Scripps’s Tom Edgington. “It’s a long path to something that helps the public and changes the world.”
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