A new DNA vaccine can pump out unprecedented amounts of flu protein into the bloodstream of mice, rendering them resistant to the flu virus. The experimental vaccine, described in next month's Nature Biotechnology, could lead to a human influenza vaccine that uses up to 1000 times less DNA than current experimental vaccines. Experts say this improves chances that the vaccine would win Food and Drug Administration (FDA) approval for use in people.
Many researchers and health officials worry that foreign DNA in a vaccine might slip into human chromosomes and interfere with their function. To minimize the amount of DNA in a flu vaccine, researchers at the Karolinska Institute in Stockholm, Sweden, turned to an alphavirus called Semliki Forest Virus (SFV). After entering a cell, most viruses produce mRNA that codes for proteins. SFV, however, has jazzed up this process by both coding for protein and churning out new copies of mRNA, which dramatically speeds up protein production. Rather than use the virus itself, the team created stretches of DNA that correspond to the RNA regions in SFV that dictate how the virus replicates. To this DNA they tacked on a gene that codes for influenza antigen.
In test-tube experiments with hamster cells, the DNA vaccine created mRNA that both copied itself like it would in the alphavirus and produced antigen. When the researchers injected the vaccine into mice, levels of antibodies and immune cells called lymphocytes were up to 1000-fold higher than in mice given conventional vaccine. They found that the alphavirus-based vaccine confers immunity to influenza comparable to a conventional DNA vaccine, but requires up to 1000-fold less DNA. Another plus is that the DNA vaccine self destructs in roughly a week, further lowering the chances that it can infiltrate chromosomes.
But it's still unknown whether the DNA will integrate into chromosomes, says John Polo, a molecular biologist at Chiron Technologies Center for Gene Therapy in San Diego, California, which is developing similar vaccines for HIV and the herpes virus. Sharply cutting DNA levels in a vaccine, he says, "might give you a very strong advantage" at avoiding integration.