Ebola is a rare but frightening disease with no cure. There are also
worries of it being used in a terrorist attack. Now, researcher Charles
Arntzen, from the Biodesign Institute® at Arizona State University,
along with colleagues from ASU, the University of Arizona College of
Medicine-Phoenix, and the United States Army Medical Research Institute
of Infectious Diseases, Fort Detrick, MD, have made interesting progress
in the search for a vaccine against the disease.
Their work, which is published in the Proceedings of the National Academy of Science, has a cutting edge approach, utilizing tobacco plants as living pharmaceutical production facilities.
The plants essentially manufacture the Ebola vaccine from a DNA blueprint in conjunction with a specially developed bacteria that is infused into the plant leaves. This approach is radically different from traditional vaccines, like that used against the flu virus, which are generally grown using animal cells, egg or yeast for a culture. Perhaps tobacco, the number one public health enemy, has a healthy use after all.
One of Arntzen's main problems that made him have to push the envelope in vaccine generation, is that outbreaks of Ebloa are infrequent, whereas other viruses like HIV that researches are working intensively for a vaccine against, have commonly occurring patterns of infection.
With Ebola being so rare and unpredictable, which is just as well, because it is such a lethal disease, making any kind of clinical trials is rather difficult. Researchers have recently been testing HIV vaccines in clusters of populations in Thailand, which has a high prevalence of the disease. However something like this is impossible with Ebola, and its rare nature makes it is more likely that the vaccine would not be used widely in an entire population, but more as a counter-measure against someone with an infection (known as passive immunization), or in a localized area to prevent an epidemic taking hold.
Testing and how to use the vaccine is not the only problem though. While it might seem that the best idea would be to create a depository of the vaccine to be used in the event of an outbreak or terrorist event, Arntzen states that despite alternatives, there are no human Ebola vaccines available. There are some promising possibilities and there have been some good results, with animals showing acceptable levels protection against the virus, but practical considerations make things difficult.
Charles Arntzen said:
The problems of testing and production are further compounded, due to the dangerous nature of the disease. Experiments had to be carried out by highly skilled researchers at a state-of-the-art bio-containment facility run by the US Army Medical Research Institute in Maryland.
Their aim was to trial the vaccine on live mice. Arntzen's vaccine was at least the equivalent of other experimental vaccines (from animal sources), achieving an 80% survival rate in mice injected with lethal shots of Ebola. Additionally, his technique of cultivation using tobacco plants means not only large cost savings in production, in part due to the ease of purifying the vaccine from vegetable rather than animal matter, but also because his product can potentially be freeze-dried and stored at room temperature.
Ease-of-storage is one of the most essential requirements of the vaccine, as it would only be used in specific situations, which might not occur for years in the future.
Arntzen's vaccine also uses a different adjuvant, an additive that increases the vaccine's potency. The FDA normally approves Alum (aluminum hydroxide), but during the tests at Maryland, mice survival rates did not show any increase. Instead, a Toll-like receptor (TLR) agonist called PIC was administered with the Ebola Immune Complex (EIC). EIC is essentially an aggregate created by fusing a key surface protein (known as GP1) from the Ebola virus with a monoclonal antibody customized to bind to GP1.
The use of Toll-like receptors is an advance in vaccine techniques from standard products. Toll-like receptors are part of the body's innate immune system, involved in processes of inflammation, where defensive cells like macrophages and dendritic cells are attracted to the site of infection.
Arntzen explains that because the TLR agonist PIC acts to mimic a site of inflammation, it amplifies the immune response, without causing tissue damage.
Arntzen said:
Ebola belongs to a class of viruses called filoviridae, due to their threadlike nature. The EIC platform may well provide a vehicle to creating vaccines against other viruses in this class, and the straightforward purification protocol might also be useful in the case of other pathogens, including hepatitis C or dengue fever, where the extraction of glycoproteins has thus far been difficult.
All in all, it would appear that Arntzen's Ebola research has pushed vaccine creation into a new era, that might even appease some of the detractors against vaccines, which in recent years have been accused of causing Autism and other problems in children.
Complaints of the use of animal sources for DNA and preservatives could be allayed by plant derived, freeze-dried vaccines, with a long shelf life.
Their work, which is published in the Proceedings of the National Academy of Science, has a cutting edge approach, utilizing tobacco plants as living pharmaceutical production facilities.
The plants essentially manufacture the Ebola vaccine from a DNA blueprint in conjunction with a specially developed bacteria that is infused into the plant leaves. This approach is radically different from traditional vaccines, like that used against the flu virus, which are generally grown using animal cells, egg or yeast for a culture. Perhaps tobacco, the number one public health enemy, has a healthy use after all.
One of Arntzen's main problems that made him have to push the envelope in vaccine generation, is that outbreaks of Ebloa are infrequent, whereas other viruses like HIV that researches are working intensively for a vaccine against, have commonly occurring patterns of infection.
With Ebola being so rare and unpredictable, which is just as well, because it is such a lethal disease, making any kind of clinical trials is rather difficult. Researchers have recently been testing HIV vaccines in clusters of populations in Thailand, which has a high prevalence of the disease. However something like this is impossible with Ebola, and its rare nature makes it is more likely that the vaccine would not be used widely in an entire population, but more as a counter-measure against someone with an infection (known as passive immunization), or in a localized area to prevent an epidemic taking hold.
Testing and how to use the vaccine is not the only problem though. While it might seem that the best idea would be to create a depository of the vaccine to be used in the event of an outbreak or terrorist event, Arntzen states that despite alternatives, there are no human Ebola vaccines available. There are some promising possibilities and there have been some good results, with animals showing acceptable levels protection against the virus, but practical considerations make things difficult.
Charles Arntzen said:
"All of these existing vaccine candidates are genetically modified live viruses ... If you've got something that you're going to have to keep at liquid nitrogen temperatures for years at a time, in hopes that there will never be an outbreak, it makes it impractical. "
The problems of testing and production are further compounded, due to the dangerous nature of the disease. Experiments had to be carried out by highly skilled researchers at a state-of-the-art bio-containment facility run by the US Army Medical Research Institute in Maryland.
Their aim was to trial the vaccine on live mice. Arntzen's vaccine was at least the equivalent of other experimental vaccines (from animal sources), achieving an 80% survival rate in mice injected with lethal shots of Ebola. Additionally, his technique of cultivation using tobacco plants means not only large cost savings in production, in part due to the ease of purifying the vaccine from vegetable rather than animal matter, but also because his product can potentially be freeze-dried and stored at room temperature.
Ease-of-storage is one of the most essential requirements of the vaccine, as it would only be used in specific situations, which might not occur for years in the future.
Arntzen's vaccine also uses a different adjuvant, an additive that increases the vaccine's potency. The FDA normally approves Alum (aluminum hydroxide), but during the tests at Maryland, mice survival rates did not show any increase. Instead, a Toll-like receptor (TLR) agonist called PIC was administered with the Ebola Immune Complex (EIC). EIC is essentially an aggregate created by fusing a key surface protein (known as GP1) from the Ebola virus with a monoclonal antibody customized to bind to GP1.
The use of Toll-like receptors is an advance in vaccine techniques from standard products. Toll-like receptors are part of the body's innate immune system, involved in processes of inflammation, where defensive cells like macrophages and dendritic cells are attracted to the site of infection.
Arntzen explains that because the TLR agonist PIC acts to mimic a site of inflammation, it amplifies the immune response, without causing tissue damage.
Arntzen said:
"In immunology, that means you've got something that is much easier for our immune system to recognize ... Because it has many copies of an identical molecule, it's called a repeating array."
Ebola belongs to a class of viruses called filoviridae, due to their threadlike nature. The EIC platform may well provide a vehicle to creating vaccines against other viruses in this class, and the straightforward purification protocol might also be useful in the case of other pathogens, including hepatitis C or dengue fever, where the extraction of glycoproteins has thus far been difficult.
All in all, it would appear that Arntzen's Ebola research has pushed vaccine creation into a new era, that might even appease some of the detractors against vaccines, which in recent years have been accused of causing Autism and other problems in children.
Complaints of the use of animal sources for DNA and preservatives could be allayed by plant derived, freeze-dried vaccines, with a long shelf life.
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