Wednesday, December 14, 2011

Who cares about smallpox anyway? The underlying dangerous of previously eradicated disease

If you are old enough to read this science blog, you have most likely encountered at least one vaccine in your life. Be it MMR whilst you were a child, or more selective vaccines like the HPV vaccine for young adult females. Perhaps you’ve always gone with the recommendations of your physician, or perhaps you just let your parents decide. But the fact remains, vaccines are a part of life in the United States and across most of the industrialized world. One vaccine that you may not have encountered, if you were born after the 1970s would be the small pox vaccine. Smallpox was one of the most deadly, although preventable, vaccines to range throughout the developed world. In the mid-1960s the WHO took a stance and aggressively fought the smallpox virus (vaccinia or Variola) with the use of an attenuated virus vaccine. In the United States the disease was claimed to be eradicated by the early 1970s and there has not been a large recorded resurgence since this time.1
Unfortunately, while we live in a society free of many diseases that underdeveloped countries still suffer from, we are not necessarily safe. There is always a constant threat of bioterism, and the use of smallpox as a live chemical agent in bioterror is a very real possibility. As more and more unvaccinated individuals are brought into society, the question of how to protect against or target this threat becomes real. Some may suggest that using the vaccine stores will work, other suggest newer methods as the way to go. The previous vaccine was made from a live virus sample that had been rendered less harmful while still providing the body with the tools to fight off infection if they were to encounter the full force pathogen.

One such group has worked to create a vaccine that does not require infection with the live attenuated vaccinia. This group has worked instead to use what they call the “genome-to-vaccine approach” to make vaccines from HLA Class 1 and Class 2 epitopes. Epitopes are the part of an antigen (the signal on the virus) that your immune system recognizes. Your immune system can recognize foreign invaders by their epitopes using antibodies, B cells or T cells (all parts of the normal functioning immune system). The authors idea in this research project is to make epitopes from the vaccinia and variola genomes that can be given to patients through vaccination and induce successful production of vaccine immunogenicity. Their work is focused around creating epitopes, recognized by the patients T cells, that are able to illicit an immune response and thus protect against exposure to vaccinia.
What they found: In order to test if these epitopes worked to illicit an immune response, researchers injected mice with different types of epitopes and followed up with booster shots. They then measured the T cell responses in mice (an indication of immune response). What they found was that T cell responses were significant in the majority of the pools of epitopes they tested. To make sure that this worked against the actual virus the researchers then infected the immunized mice with smallpox and found that 100% of mice who had been given the epitope vaccine survived, while the mice without vaccination only had 19% survival. This is important because this means research is able to both provide direction for future smallpox vaccines and introduce information about the immune system.
As such, the future implications of this work would entail figuring out why exactly these epitopes are causing a T cell response instead of the conventionally thought B cell recognition. Additionally the researchers would need to take further steps towards getting their product on the market. While initial results are promising, these results will have to be duplicated, and tested through various routes before it is ready for human trial. However, the fact remains that there is promise in vaccine methods that don’t require the use of the whole “live” virus. This will be increasingly important to explore in areas of the world where there are both highly immunocompromised populations, and where smallpox is prevalent.

Primary Resource
Moise L, Buller R M, Schriewer J, Lee J, Frey S, Martin W, De Groot A S. (2011). VennVax, a DNA-prime, peptide-boost multi-T-cell epitope poxvirus vaccine, induces protective immunity against vaccinia infection by T cell response alone. Vaccine. 29: 501-511.
Other Resources
1. "Smallpox" World Health Organization.

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