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Virus-Like Particles May Mean Speedier Flu Vaccines
We've been talking a lot lately about flu vaccines. Now an anonymous reader sends us to a Technology Review piece on two human trials involving so-called virus-like particle vaccines, which promise to be much faster to churn out than traditional vaccines. (Here's a single-page version but without the useful illustration.) VLP vaccines use a protein shell, grown in either plant or insect cells, that look just like real viruses to the body's immune system but that contain no influenza RNA genetic material. A company called Medicago grows its VLPs in transgenic tobacco plants, while another called Novavax uses "immortalized" cells taken from caterpillars. Providing they pass safety muster, both techniques should be able to produce an influenza vaccine more quickly than current methods, using just the DNA of the virus.
Although influenza is an RNA virus, researchers are probably generating a cDNA library of the flu structural proteins and using these DNA templates to transfect their cellular expression systems, resulting in the production of the virus-like particles. This may be the source of confusion in the summary above.
This solution would probably require much higher doses than current vaccines do, but it would probably be safer and faster.
The flu at least is an RNA virus, but the function of the genetic material is for the replication of the virus after it has infected a cell. When it is not actively infecting a cell the DNA/RNA is completely dormant within the viral coat, thus the debate over whether viruses are alive or not. There is no metabolic activity in the absense of a host cell to infect.
The shell or viral coat is primarily what the immune system recognizes when fighting a viral infection. That is why killed vaccines work. They don't work as well as modified live vaccines (generally) because you don't get the first couple of generations of viral replication (at a slower rate than the wildtype virus) that trigger a much stronger immune response. Viral RNA can also trigger immune response, but the RNA needs to be processed by an antigen presenting cell such as an infected cell or a phagocyte.
It actually works the same way with certain bacteria. Researchers will frequently inject LPS (lipopolysaccharide) into animals to simulate a bacterial infection, because bacteria have LPS on their surfaces and their are immune systems designed to recognize this ubiquitious bacterial component.
I'm not sure about separate shells, but I do know that many (all?) viruses have several different proteins involved in making the shell, and that changes in which proteins are present will change the antigenic profile of the virus.
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Serious side effects from vaccination are on the order of one in a million or less, serious disease from the flu is on the order of one in thousand or more.
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Most flu vaccines are inactivated. On the other hand, "live attenuated influenza vaccine" is reduced in virulence but still "alive", and "may cause an infection with complications in people with weakened immune systems or other underlying medical conditions."
http://en.wikipedia.org/wiki/Live_attenuated_influenza_vaccine#Risks
For standard flu vaccines, the speed of production depends on quite a few steps, some of which can be carried out in parallel (e.g. clinical trials can start before all batches are made), while others need to be done in series (e.g. bulk production can't start until growth conditions are optimised):
http://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090806/en/index.html
One advantage of the VLP approach is that you can produce the relevant proteins in standard biotech 'factory' organisms, which avoids the laborious and time-consuming process of culturing live virus in hens' eggs. Reverse-transcribing the viral RNA is no big deal - this happens in the initial phase of characterising a new virus in any case (for sequencing etc.) long before vaccine production begins.
The nasal spray version of the vaccine does contain live virus, but "attenuated" so that it can only reproduce in the lining of the nose.
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http://www.masshightech.com/blog/2009/09/25/antigen-express-synthetic-h1n1-flu-vaccine-in-the-works/