Contributed by Guest Blogger: S. Goldberg ’14
Ebola Virus (EBOV) is a fairly new infection of the Filoviridae family, that causes Ebola Hemorrhagic Fever, or EHF. This infection can often be severe or fatal in humans and primates. Because it would be difficult to create a vaccine against all four different virus species of Ebola, scientists came up with a plan to develop a vaccine protective against a single species of the infection. An experiment was designed to test to see if a “prime-boost” strategy would work, with a vaccine protecting against one Ebola Virus species and protecting a different species at the same time. In the process of doing this experiment, it was found that the vaccine developed to protect primates against the two most lethal Ebola Virus species also protected against the newer Ebola virus species that was founded in 2007. The prime-boost vaccination provides immunity against newly emerging EBOV species and shows cross-protection against EBOV infection. In this strategy, the “prime” is a DNA vaccine that has a small amount of genetic material with surface proteins of the Zaire Ebola virus species and the Sudan Ebola virus, the two most lethal species of EBOV. The “boost” is made of a weak cold virus that delivers the Zaire EBOV surface protein. The experiment, conducted and overseen by the National Institute of Allergy and Infectious Diseases and the US Army Medical, gathered eight 3 to 5 year old cynomolgus monkeys as their test subjects, to see if such a vaccine actually protected against the two older Ebola virus species and the newer strain. Each of the monkeys were given the immunization and then transferred to a laboratory where they were exposed to the EBOV infection. The monkeys stayed their for the duration of the experiment. Using a blood analyzer, liver enzyme levels were examined on “days 0, 3, 6, 10, 14, 21 and 32”. During this test, samples of T-cell intracellular cytokines were taken. CD8+ T-cells were stained with antibodies, against intracellular cytokines. This technique allows for the frequency of antigen-specific T-cells to be determined. The production of cytokines plays an important role in the immune response of the body. After isolating the RNA of each subject, each of the monkeys given a vaccine that contained Zaire EBOV and Sudan EBOV glycoprotein (GP). After the GP was exposed within each of the bodies, the subjects developed “robust antigen-specific…immune responses against the GP from [Zaire EBOV] as well as cellular immunity against lethal…[Bundibugyo EBOV]”. After concluding this experiment, scientists have learned that current vaccines that can bring about T-cell immunity will have a greater possibility of “protecting against other [new] pathogenic EBOV species”.
If we have the ability to protect against new and emerging EBOV species, does that mean that, in the long-run, mutation of the virus will stop? Will existence of any EBOV species disappear? If it disappears, could it reappear? Could similar experiments be done to discover if a other currently used vaccines, aside those that display T-cell immune responses, are protecting against other unknown or new viral strains?
This sounds very interesting, but would this only apply to viruses that are very closely genetically related to one another? For instance, would it still have any effectiveness against an Ebola virus that came into being 20 years from now? Still, it is always very fascinating to see solutions to rapidly evolving viruses such as Ebola and Influenza.
The fact that researchers are able to produce vaccines in this manner is remarkable. Though the concept of using a DNA vaccine to force the body to create only surface proteins is not very innovative in itself, the fact that we are able to create these things in enough quantity to consider their mass distribution is indicative of the progress that has occurred in modern biology.
There isn’t anything new about prime-boost itself (many vaccines require booster shots) but the strategy of using the DNA vaccine to prime and a different kind of vaccine to boost is newer and gaining ground as an effective approach. You’ll remember the universal influenza vaccine I posted about earlier uses a similar approach. An HIV vaccine that showed a little bit of promise also uses this strategy.
This is a very big discovery, one which has implications even beyond the fact that it may provide an adequate solution to one of the worst modern viral epidemics. If the prime-boost method works in creating a generalized immune response to Ebola, could it work for other viruses with numerous variants too, like influenza or adenovirus? This looks poised to be the one of the primary virus-fighting methods of the future.