Saturday, December 3, 2016

Genetic modification of Influenza A virus reveal a novel vaccine production strategy

Researchers have developed a new type of vaccine. By genetically modifying the genome of Influenza A virus to require a non-standard amino acid (Ne-2-azidoethyloxycarbonyl-L-lysine which has been used in synthetic biology previously) that some microbes use. What makes this amino acid unique is its codon (three base RNA sequence that signals what the amino acid should be). In most organisms, the codon used (UAG) is actually what is known as a stop codon (it stops production of the protein chain), so this means that any gene that contains that codon will stop prematurely unless grown in an organism with that non-standard amino acid. A lot of work went into finding places in the viral protein that the non-standard amino acid could be inserted without interfering with the function of the protein. Once several sites were identified, the researchers grew the virus in kidney cells that had been genetically modified to use the non-standard amino acid. The end result was genetically stable progeny viruses that required the non-standard amino acid.

When the altered influenza virus was injected into mice, it did not replicate and the mice developed a strong immune response to the virus. Researchers were able to safely inject the mice with a dose of the modified virus that was about 100,000 times the dose of the wild-type virus that would kill half of the mice injected (LD50). The modified virus also interfered with the wild-type influenza virus in co-infections of the two.  

The implications for this development could be astounding. With this, researchers could develop a vaccine that uses a fully infectious virus that has been modified to need this amino acid to replicate. However, caution is warranted at this point. A lot of work still remains to develop this into a functional vaccine. It must go through further trials to see if it works in primates and then there are all the human clinical trials that are needed. This work is promising and certainly should be pursued further.

This negative stained transmission electron microscopic (TEM) image shows recreated 1918 influenza virions that were collected from supernatants of 1918-infected Madin-Darby Canine Kidney (MDCK) cells cultures 18 hours after infection. Photo credit: Cynthia Goldsmith courtesy of the CDC.