A “rewritten” flu virus prompts an identical immune response in mice to a natural infection – meaning it could make a more effective vaccine than traditional options.
The new vaccine virus contains exactly the same proteins as the flu strain it targets, with one major difference: its genome has been rewritten to produce a virus that replicates too slowly to cause any trouble.
“It’s unlike anything nature ever evolved,” says Steffen Mueller, a virologist at Stony Brook University in New York, whose team tested the vaccine in mice.
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The team exploited a quirk in the genetic code to weaken the virus without changing the proteins it contains. Three-letter DNA sequences called codons determine which amino acids get assembled into a protein. Yet with more three-letter combinations than there are amino acids, more than one codon can produce the same amino acid.
Organisms have their favourites – preferring some codons over others because they translate into proteins more efficiently, says Mueller.
His team took advantage of this quirk to engineer a flu virus that contains thousands of genetic alterations that result in unfavourable combinations of codons. “We call this death by one thousand cuts,” says Mueller. Each alteration is virtually inconsequential by itself, but together they create a weakened virus that does not replicate well.
Mice that were given the vaccine stayed healthy. After four weeks, they were infected with a dose of flu that would ordinarily kill them. Three days later, 80 per cent of the mice had no detectable flu virus in their system (Nature Biotechnology, ).
The rewritten virus should elicit a stronger immune response than traditional vaccines because it would expose the immune system to proteins identical to the ones seen in seasonal or pandemic flu strains, says Mueller.
“It’s an interesting approach to flu vaccination and is certainly likely to be safe,” says of the University of Oxford.