Progress made toward a vaccine for Ebola

has many copies of an identical molecule, it’s called a repeating array.”

Within two weeks after the vaccine “blueprint” is delivered to tobacco leaves, enough of the EIC accumulates to allow its purification from other leaf cell components. The researchers then vaccinated mice with the purified sample, and showed that their immune system gave a strong response.

For the ultimate validation of the vaccine however, it was necessary to show that the vaccinated mice could withstand an Ebola virus infection. Because of the dangers in handling the virus, these experiments were conducted by skilled researchers at a high containment facility operated by the US Army Medical Research Institute in Maryland. It was found that the level of protection of the vaccinated mice was equivalent to that seen in prior experiments with the best, previously available experimental vaccine.

The advantages of using tobacco to manufacture a vaccine are significant. The initial costs for plant growth are much cheaper than design of traditional pharmaceutical facilities. In addition, the material extracted from tobacco leaves can be easily purified, and then might be spray dried or freeze-dried, yielding a highly stable compound, storable at ambient temperatures for extended periods. This will be essential for an Ebola vaccine, since it will primarily be stockpiled to use only if there is a disease outbreak.

Vaccines typically contain adjuvants — immune modulating factors that improve a vaccine’s protective qualities.

Most vaccines contain alum (or aluminum hydroxide), which is an FDA approved adjuvant. In the case of the plant-derived Ebola vaccine, alum did not improve the survival rates in mice when it was co-administered with EIC.

Instead, the group found that a Toll-like receptor (TLR) agonist known as PIC, when delivered in tandem with EIC, dramatically improved survival.

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 the TLR agonist PIC acts to mimic a site of inflammation, amplifying the immune response, without causing tissue damage. In experiments using a combination of PIC and EIC, mice achieved an 80 percent survival rate against a lethal challenge of Ebola — commensurate with the best existing vaccine candidates.

The road ahead
In their companion PNAS paper, Arnzen’s collaborators at Mapp Biopharmaceuticals outline the process for creating the monoclonal antibodies used for this research. Treatment for an Ebola infection, Arntzen says, would likely involve the injection of fast acting antibodies to attack the virus directly — a process known as passive immunization, combined with a vaccine to stimulate the protective immune response (active immunization). This approach is commonly used in the case of other viral infections, particularly rabies. “Our two papers offer a nice back to back picture,” Arntzen says. “We can manufacture both of these post-Ebola exposure reagents for a defensive stockpile, using tobacco.”

The next steps for a plant-derived filovirus vaccine will involve using the EIC platform to design protection against the full range of these threadlike viruses. The method, with its straightforward purification protocol might also be used in the case of other pathogens including hepatitis C or dengue fever, where the extraction of glycoproteins has thus far been difficult.

Should efforts succeed in producing a post-exposure therapeutic that could be stockpiled by the U.S. military, the vaccine could also be made available to the Center for Disease Control for immediate use in the event of a remote outbreak.

— Read more in Waranyoo Phoolcharoen et al., “A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge,” Proceedings of the National Academy of Sciences (5 December 2011) (doi: 10.1073/pnas.1117715108)