MIT engineers have developed programmable RNA vaccines that can be manufactured in one week, allowing it to be rapidly deployed in response to disease outbreaks. So far, they have designed vaccines against Ebola, H1N1 influenza, and Toxoplasma gondii (a relative of the parasite that causes malaria), which were 100 percent effective in tests in mice.
The RNA vaccines consist of strands of genetic material known as messenger RNA, which can be designed to code for any viral, bacterial, or parasitic protein. These molecules are then packaged into a molecule that delivers the RNA into cells, where it is translated into proteins that provoke an immune response from the host.
In addition to targeting infectious diseases, the researchers are using this approach to create cancer vaccines that would teach the immune system to recognize and destroy tumors.
“This nanoformulation approach allows us to make vaccines against new diseases in only seven days, allowing the potential to deal with sudden outbreaks or make rapid modifications and improvements,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
Most traditional vaccines consist of an inactivated form of a virus or other pathogen. These vaccines usually take a long time to manufacture, and for some diseases they are too risky. Other vaccines consist of proteins normally produced by the microbe, but these don’t always induce a strong immune response, requiring researchers to seek an adjuvant (a chemical that enhances the response).
RNA vaccines are appealing because they induce host cells to produce many copies of the proteins they encode, which provokes a stronger immune reaction than if the proteins were given on their own. The idea of using messenger RNA molecules as vaccines has been around for about 30 years, but one of the major obstacles has been finding a safe and effective way to deliver them.
By customizing the RNA sequences, the researchers can design vaccines that produce nearly any protein they want. The RNA molecules also include instructions for amplification of the RNA, so that the cell will produce even more of the protein.
The vaccine is designed to be delivered by intramuscular injection, making it easy to administer. Once the particles get into cells, the RNA is translated into proteins that are released and stimulate the immune system. Significantly, the vaccines were able to stimulate both arms of the immune system — a T cell response and an antibody response.
In tests in mice, animals that received a single dose of one of the vaccines showed no symptoms following exposure to the real pathogen — Ebola, H1N1 influenza, or Toxoplasma gondii.
The researchers also believe that their vaccines would be safer than DNA vaccines, another alternative that scientists are pursuing, because unlike DNA, RNA cannot be integrated into the host genome and cause mutations.
The ability to rapidly design and manufacture these vaccines could be especially beneficial for fighting influenza, because the most common flu vaccine manufacturing method, which requires the viruses to be grown inside chicken eggs, takes months. This means that when an unexpected flu strain appears, such as the 2009 pandemic-causing H1N1 virus, there is no way to rapidly produce a vaccine against it.
The research was funded by the Department of Defense Office of Congressionally Directed Medical Research’s Joint Warfighter Medical Research Program, MediVector Inc., the Ragon Institute of MGH, MIT, and Harvard, and the Defense Threat Reduction Agency/Joint Science and Technology Office program in vaccines and pre-treatments.
Image: MIT News