Nov. 28, 2008 A new vaccine principle is being developed by scientists at the University of Copenhagen which -- if it works to its full expected potential -- could help to save millions of lives and revolutionise current vaccine technology.
The ‘InVacc' platform, as it is known, represents an advance on the original DNA vaccines and generates new vaccines with greatly enhanced properties. The platform consists of a chain of amino acids attached to a gene of the virus being vaccinated against. This genetic cocktail is then inserted into an incapacitated flu-like virus such as the adenovirus and injected into the body, where it triggers a broader and more aggressive immune response, enabling the immune system to quickly seek out and destroy the disease when it invades.
"We are extremely excited to be working on the vaccine technology", says Associate Professor Jan Pravsgaard, the lead scientist behind the project. "The platform has proved very effective in our recent tests and could have enormous potential. In principle, vaccines of this type could be used to inoculate against a range of deadly viruses, bacteria and other disease-causing agents and even be used to cure certain cancers once they take hold."
Tests of the vaccine platform on mice so far look extremely promising with the scientists able to provide 100% protection against different, lethal strains of flu given to the test animals.
The scientists also believe that the new vaccines will be effective despite the ability of different viruses and bacteria to constantly mutate and develop resistance.
How the new technology works
The original DNA vaccines - the precursor of the present platform - consist of a single gene taken from the virus or bacteria against which protection is sought and is injected into the body. The alien DNA is then ‘read' by the body's host cells (transcription of the gene) and is converted into pathogenic proteins. Because these pathogenic proteins (antigens) are recognised as foreign, they are placed on the surface of the cell to alert the immune system and trigger an appropriate immune response. This, at least is the idea behind the original DNA vaccines, which use the more potent ingredient of a gene rather than live, biological material to activate the immune system.
DNA vaccines, however, have so far been ineffective because, in practice, they generate too few of the all-important antigens - the ‘alarm bells' that warn the immune system of attack. This is because DNA vaccines are unable to fully decode their contents and deliver their message to the immune system. In other words, the original DNA vaccines are unable to guide the body to ‘read' and process the particular cell pieces that are carrying the DNA vaccine, which in turn would ensure that the antigens are produced.
The scientists behind InVacc, however, have come up with a means to overcome this problem. Their key innovation - the chain of amino acids inserted into the adenovirus - promotes the decoding of the new vaccines and ensures that more of the antigens are shown to the immune system. The adenovirus used for the vaccines plays a crucial role in all of this because it helps to set off the necessary chain reaction that allows the vaccine platform to work. It does this by presenting the body with a recognisable threat. ‘Primed' to react to the adenovirus, which it has been exposed to many times before, the body becomes more sensitive to and hones in on the particular pieces in the body that are carrying the adenovirus (with the DNA vaccine concealed inside) and begins processing these cell pieces.
The second important component in the vaccine platform, the amino acid chain, is now also able to work and is critical to providing long-lasting immunity from disease. The chain, made up of 215 amino acids, functions to latch onto and drag up more of the important genetic material from the vaccines to the surface of the cells, thereby ensuring that more antigens are exhibited. The greater the amount of material raised to the surface from the vaccines, the more likely that the right attack cells are activated.
"The delivery mechanism provided by the amino acids is important for several reasons", explains Associate Professor Pravsgaard. First, the amino acid chain enables the vaccines to activate different profiles of attack cells. Second, it picks up more of the important genetic information from the inner compartment of the virus or bacterium - where for our purposes - the crucial DNA material is based. Attaching DNA strands from the interior of the virus to the amino acid chain is crucial to developing stable vaccines, since it gives the immune system solid data on the nature of the threat it is faced with, even after the virus or bacteria has mutated".
Deadly pathogens such as viruses tend to mutate when they replicate and are thus able to pass under the radar of the immune system and avoid detection. "A mutated virus is a bit like a virus wearing a disguise," explains Professor Pravsgaard. "Viruses possess a special protein surface or outer shell that they constantly adapt to protect their core DNA from being damaged. However, if we can give the immune system more intelligence about the virus from its conserved interior - which is less likely to mutate - we can then communicate the true identity of the virus. It's as if we were giving the immune system a fingerprint of a criminal with several points of identification, so that it can recognize the virus, regardless of its disguise".
The scientists from the University of Copenhagen predict that the new platform will protect against the vast majority of viruses and bacteria, where a gene can be identified and targeted with a DNA vaccine. Certain cancers such as skin cancer which have a genetic basis and/or a viral profile (e.g. cervical cancer begins with infection by the human papillomavirus) would also be candidates for the vaccines.
The Scandanivan company Novo A/S and the Novo Nordisk Foundation have such faith in the new technology that they have already invested funds to create a strategic plan for development and use of the vaccine. "The grants awarded through our Novo Seeds programme are only for very select projects that show outstanding promise, explains Novo Seeds Investment Director, Stephen Christgau." "InVacc is definitely one of those. Our grants will help the team to develop and commercialise their groundbreaking research and validate the advantages of the vaccine platform against competing technologies".
Peter Holst from the research team (together with the Technical Transfer Unit) is currently also seeking backing from international funds to take the project to its next phase of development and ultimately into clinical trials.
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