What’s in the Needle #2: Rabies and Ebola Combined

[Y]ou might wonder whether or not I’ve added rabies just to put a ‘scare’ in my readers, but the truth is that the DoD, the NIH, NIAID, and Thomas Jefferson University have teamed up to produce a genuine vaccine candidate built on the rabies vaccine.

In a way, it makes sense. In Africa, many animals contract both rabies and Ebola and can spread both diseases to human through a bite. And until recently, very few with deep pockets felt inclined to put their investment dollars into a vaccine that might be used or not (vaccines do have a shelf life). Let’s face it, most pharmaceutical companies prefer to make a profit, and their investors expect one, so it makes selling the idea much easier if you can guarantee sales year after year. Rabies vaccines must be repeated every 1-2 years (at least in our dog they do), so it’s probable that wildlife managers and zoos would line up to buy something that protected against rabies and filoviruses.

So, how is a rabies vaccine going to work against Ebola—a very different type of virus. Put simply, it has to be genetically modified, which makes this a recombinant vaccine.  Dr. Joseph Blaney who works for the NIAID (National Institute of Allergy and Infectious Diseases) is listed as a lead author on some of the research that first appeared in publication around August, 2011 (I say ‘around’ because this is the earliest version I could find online, but I’m not precluding and earlier publication). Another researcher on the project is Dr. Peter Jahrling, one of the giants in filovirus research—and a name familiar to anyone who has read ‘The Hot Zone’. These two along with many other diligent researchers have found what appears to be a ‘bivalent’ (confers immunity for two serotypes) vaccine with income potential, which means it might actually be produced.

To create their little chimera, the researchers took what is called an attenuated rabies virus. Attenuated means that it has been altered so that it is weak, less vigorous. The Ebola/Rabies vaccine uses a recombinant version of this attenuated virus. This virus is derived from the current rabies vaccine by reverse engineering the vaccine to produce a rabies virus genome. The rabies virus is spliced with a gene that causes it to produce Ebola glycoproteins on its surface. Both rabies and filoviruses like Ebola and Marburg have an outer envelope that is derived from the previous victim’s cells (or from cells in your own body). When the virus approaches a new cell, the glycoproteins do a sort of ‘handshake’ with exterior proteins on that cell’s membrane, and since the virus is dressed appropriately, the victim cell says ‘come on in’ and commences a process called endocytosis (bringing the virus in through the door). Glycoproteins (GPs) are produced by the host cell along with all the other virus products: the virus cannot reproduce on its own, it must hijack your cells and force them to make copies of its RNA genome and all the proteins required to make new virus particles.

The Rabies/Ebola vaccine candidate expresses Ebola GPs on its outer surface, making it look just like an Ebola virus, training the host body’s immune system to recognize the trickster. According to the research, both the IgG and complement systems within the body are activated. It is not known yet whether or not T-cell activation occurs. IgG is a type of immunoglobulin (an antibody), and the Complement System consists of 20 types of cells that circulate through the blood system on the lookout for invaders. Complement cells are amazing inventions (thank you, Lord), because they’re in two parts. When a complement cell sees an invader, it attaches to the invader or to an exposed portion of IgM or IgG (if antibodies are even involved), and it then splits in half. Half stays with the invader, and the other half runs out to gather re-enforcements.

According to published research on the Rabies/Ebola vaccine candidate, not only does the recombinant (rRAB) vaccine induce an immune response in mice and monkeys, it is likely to do the same in humans.

In his speech before Congress, NIAID head Dr. Anthony S. Fauci, said this about the rabies vaccine candidate:

NIAID intramural scientists are collaborating with Thomas Jefferson University investigators to produce a vaccine candidate based on an existing rabies vaccine. The researchers aim to generate immunity to Ebola, Marburg, and rabies viruses, important diseases in certain regions in Africa. The investigators plan to pursue a version of the vaccine for human and veterinary use, as well as a version for use in African wildlife. The wildlife vaccine could help prevent transmission of Ebola virus from animals to humans. The vaccine candidate for use in humans is undergoing preclinical testing and has demonstrated protection against infection by rabies and Ebola viruses in animal models. NIAID is currently partnering with DOD to produce sufficient quantities of the vaccine candidate to begin clinical testing in 2015. In September, NIH licensed the candidate rabies/Ebola vaccines to Exxell BIO of St. Paul, Minnesota, which aims to advance the products through clinical testing and potential commercialization.[i]

You can find the announcement of the proposed partnership between the NIH, HHS, NIAID, and Exxell Bio online. Here is the summary:

This is notice, in accordance with 35 U.S.C. 209 and 37 CFR 404, that the National Institutes of Health (NIH), Department of Health and Human Services (HHS), is contemplating the grant of a an exclusive license to practice the following invention as embodied in the following patent applications: E-032-2011/0, Blaney et al.,“Multivalent Vaccines for Rabies Virus and Filoviruses,” U.S. Patent Application Number 61/439,046, filedon February 3, 2011, PCT Application Number PCT/US2012/23575, filed on February 2, 2012, U.S. Patent Application Number 13/983,545, filed on August 2, 2013, European Patent Application Number 12702953.6, filed on February 2, 2012, and Canadian Patent Application Number 2826594, filed on February 2, 2012, to Exxell BIO, Inc., having a place of business in Shoreview, Minnesota, United States of America. The patent rights in these inventions have been assigned to the United States of America and Thomas Jefferson University.[ii] [emphasis added]

I’ll bet the taxpayers of the US won’t see a dime of any profits made from the sale of this vaccine, if it makes it past clinical trials—which is very likely considering the current Ebola outbreak. Oh, the date the above was published was in March of this year.

A press release about the partnership to produce enough vaccine for a large clinical trial had a bit more to add:

The experimental vaccines—based on rabies virus vaccines currently used in people and in animals—contain either a killed or a live, attenuated (weakened) rabies virus engineered to produce an Ebola protein. The killed, or inactivated, vaccine is being developed to prevent rabies and Ebola infection in people, while the live, attenuated vaccine is intended for use in African wildlife to help prevent Ebola virus transmission from animals to people.[iii] [emphasis added]

Now, here is where it gets tricky. If the virus candidate can contain either live or weakened viruses, then let’s just pray that the batches are never, ever mixed up. Personally, I prefer not to have a live rabies virus inserted into the arms of anyone I love. But more to the point, what might the live virus do in field trials within animal populations. Viruses love to mutate. With all the movies about a mutated rabies virus in theaters, it does give one pause—or paws. But let’s always remember, no matter what happens in the world, we can be certain that our Savior Jesus Christ is always an infinite number of steps ahead of science.

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[i] http://docs.house.gov/meetings/IF/IF02/20141016/102718/HHRG-113-IF02-Wstate-FauciA-20141016.pdf

[ii] https://www.federalregister.gov/articles/2014/03/31/2014-07023/prospective-grant-of-exclusive-license-multivalent-vaccines-for-rabies-virus-and-ebola-and-marburg

[iii] http://www.news-medical.net/news/20141017/NIAID-announces-license-agreement-to-develop-dual-purpose-candidate-vaccines-for-rabies-Ebola.aspx