A team of molecular biologists and computer scientists have used a new method to weaken the influenza virus by designing hundreds of mutations to its genetic code to create an effective vaccine. The method, published in the journal Nature Biotechnology, may be a major step in developing more effective and safe vaccines against influenza.
The research team at Stony Brook University first synthesized and generated the polio virus in 2002. From there, they designed and synthesized a new class of attenuated polio viruses. Viruses attenuated by traditional means often make effective vaccines but sometimes mutate to regain virulence. The creation of synthetic viruses nearly eliminates the possibility of the virus regaining virulence.
In their latest research, the team used the same method to design an influenza vaccine. The vaccine was found to be effective and safe against influenza in mice.
“Essentially, we have rewritten the virus’ genetic instructions manual in a strange dialect of genetic code that is difficult for the host cell machinery to understand,” says Steffen Mueller, PhD, senior study author and research assistant professor of molecular genetics and microbiology at Stony Brook. “This poor line of communication leads to inefficient translation of viral protein and, ultimately, to a very weak virus that proves to be ideal for immunization.”
The researchers made a synthetic influenza virus (strain A/PR/8/34) containing hundreds of changes in its genetic code. The changes they chose are commonly referred to as “silent” mutations because they do not alter the proteins that the virus produces. However, through computer algorithms developed by the researchers, mutations were arranged such that the resulting viral genome will produce less of these proteins, a process called “de-optiminization,” or a weakening of the virus.
The researchers believe the process, called “Synthetic Attenuated Virus Engineering,” or “SAVE,” can be applied to any emerging influenza virus strain. If shown to be applicable to influenza in humans, the SAVE method could become a tool in developing effective vaccines against seasonal and pandemic influenza threats.