Programming Moves from Computers to Vaccines
Programmable vaccines sounds like something out of a science fiction movie, but the idea has been around for more than 30 years. Although the concept has always had merit, engineers have been struggling to find a way to deliver this revolutionary treatment effectively and safely. Instead of using an inactive form of a virus, or proteins produced by the microbe, the new vaccines use messenger RNA molecules.
At the same time, scientist are doing research into DNA vaccines as an alternative. DNA can however cause mutations when it is integrated into the host genome, something that can’t happen with the RNA alternative.
Khan and Chahal, the MIT researchers at the forefront of this new RNA development, have already used this method to design vaccines against H1N1 influenza, Toxoplasma gondii (a parasite similar to the one causing Malaria) and Ebola. Test in mice using these variations were 100 percent successful. Although cancer vaccines have not yet been developed using messenger RNA molecules, work in this important area has already been started.
Whereas the manufacturing time for traditional vaccines is often long, the new type can typically be supplied within one week. This is because they can be customized relatively easily. In cases of disease outbreak, this rapid deployment is only one of the many benefits of the new vaccine. Where older type vaccines are too risky for some diseases, and sometimes don’t stimulate a strong immune system response, these inefficiencies have also been addressed. Mice that were given a single dose vaccine and then exposed to the real pathogen, showed no symptoms of the disease at all!
Messenger RNA (strands of genetic material) can be coded for any bacterial parasitic or viral protein. Once the RNA is delivered into cells by a molecule it is packaged into, it translates into proteins, which in turn causes the host’s immune system to respond.
For the package molecule, Khan uses dendrimer – a branched molecule that is used to create a nanoparticle. As RNA has a negative charge, and the nanoparticle can be given a positive charge temporarily, the two form a close association. The final structure’s size and structure is carefully controlled and induced to fold over itself many times. This results in the vaccine particles becoming spherical with a diameter on only 150 nanometers – the same size as many viruses. Viruses exploit specific surface proteins to enter cells and the vaccine molecules can now do the same.
Vaccines producing virtually any protein can be designed simply by customizing the RNA sequences. The cell will produce more of the protein as the RNA molecule instructs the RNA to be amplified.
The vaccine is easily administered by intramuscular injection. The immune system is stimulated by the RNA translating into proteins when reaching the cells. The immune system employs two types of responses – an antibody response or a T cell response. It is significant to note that both these responses are triggered by the RNA vaccines. Khan notes that this happens irrespective of which antigen was picked.
In addition to the double trigger RNA vaccines stimulate, cells are induced to produce many more copies of the specific protein than would be the case with traditional protein based vaccines. Combined, these factors result in the RNA vaccines packing a powerful punch indeed.
Rather than being limited to the treatment of “exotic” diseases, the speed at which these vaccines can be designed and produced will revolutionize the fight against influenza. Currently, flu vaccines are grown inside chicken eggs and this process takes months. When new flu strains appear and become pandemic as happened with the H1N1 virus in 2009, vaccines against it could not be designed and manufactured rapidly.
For cancer vaccines, Khan uses a different approach. Certain genes that are dormant in adults and are turned on during embryonic development, often reactivate later in life and become non-small cell lung tumors. The cancer tumors will be destroyed by the immune system once the vaccine has taught it to recognize them.
What does the future hold for Khan and Chahal?
They have their sights set on Lyme disease and the Zika virus in addition to working on cancer vaccines. Rather than continuing this work for MIT, they plan to commercialize this technology and license it through their own company.
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