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COVID-19 is the biggest event of the year with an enormous effect on the world’s economic health and public well-being. This virus will ultimately be defeated by a vaccine which should be generally available in the next 12-18 months.

There is a race on among at least 83 vaccine manufactures as to who will get to the market first and who will have the most efficacious vaccine. We at Transalgae have a unique platform to tackle this problem. Our plan is to put a piece of the spike viral protein pictured above inside our favorite algal species, grow the algae out to commercial quantities and then give an algae pill with the vaccine inside.

In effect, we are using a genetically modified algae to both manufacture the spike protein and provide a natural encapsulation. The reason one receives an insulin shot or a COVID-19 vaccine in the form of an injection, is that it is difficult to protect the protein of interest from our stomach acids. In addition to protecting the protein, the algae also make the vaccine.

ADVANTAGES OF ORAL DELIVERY

Oral delivery, if efficacious, has many advantages over injections. 1) People would prefer to swallow a pill rather than receive a shot. There is unlikely to be swelling, redness, or rashes. 2) Administration is vastly simplified. No need for a nurse or other trained practitioner. No need to potentially crowd into an area to receive a shot 3) Our bodies ingest many types of bacteria and viruses every day and our digestive systems are designed to eliminate them. An injection is at greater risk of inadvertent contamination due to the manufacturing process. 4) Algae cells do not attract mammalian bacteria and viruses. Regular vaccines use mammalian cells for production and those bacteria are dangerous for humans. 5) Poorer countries do not have the refrigeration capabilities that we have and have a shortage of trained health care professionals. For those countries, an oral vaccine is the difference between having a vaccine and not having a vaccine. 6) And the final advantage concerns the vaccination technique which some of the 83 competing vaccines share with ours. Instead of using a whole dead, or live attenuated virus, we are following the subunit strategy. We have identified a portion of the spike protein pictured above and are using its insertion in algae and subsequent ingestion to generate antibodies and an immune response. This is inherently safer since most of the virus (especially that part dealing with its reproduction) is missing from the pill.

HOW TO TURN ALGAE INTO A VACCINE

We start with the sequenced genome of the COVID-19 virus. Here is a published list of its amino acid sequences. The 22 different amino acids are stitched together to make all proteins. And prior to those amino acid sequences are the base pairs which make up the DNA of the virus. We have chosen one portion of one of the genes listed above that we think will best generate an immune response in a human. It is a part of the spike protein which you can see above.

In order to cause our algae to make the desired portion of the spike protein, we have to use the alga's own codon usage table. A codon is a 3 base pair grouping that call for one of the 22 amino acids. To these base pairs needed to create the gene of interest (the spike protein), we add a promoter which tells the alga how many times to create the spike protein and a selection marker which enables us to figure out which algae have been transformed.

Next we synthesize the DNA sequence and then use a PCR machine to multiply the sequence many millions of times. We add the DNA sequence into millions of algae cells spread on plates.

This is where the selection marker mentioned above comes in. It enables us to figure out which algae were transformed. As part of the DNA which just entered the algae, we have included a gene which changes the metabolism of the algae IF it lands in the genome. We use this metabolic difference to select those algae which have been transformed.

Our next step is to grow out the selected algae in petri dishes. Eventually they become large enough for us to test to see the quality of the transformation. We will choose the best transformant for our problem. We want high expression levels plus an intact and functional form of the protein of interest – the spike protein. We want our protein to fold in the same way that the virus’ spike protein folds so that when ingested the algae’s spike protein creates useful antibodies then ready for the true corona virus.

We then grow out the algae in a fermenter in order to generate enough product to perform studies on mice fed the algae. First thing we hope for is that the spike protein shows up in their blood. Much of the algae passes through the digestive system without entering the blood stream, but the hope is that enough enters to create an immune response.

We have evidence it does so from previous studies with other proteins. We were able to immunize fish against a water-borne virus. We were able to selectively kill insects with a protein which only acts against insects (no effect on humans) and we put in an RNAi, an interfering RNA, which knocked out an insect protein, killing the insect. In mice studies, we found the protein of interest in the mouse blood and the mouse liver.

The technology was tested and approved by top global animal health and crop protection companies. Transalgae’s patents regarding oral delivery of proteins and edible vaccines are granted in the major markets worldwide.

Our next step is to see if the mouse then forms antibodies against the spike protein. There are other studies to understand dosing better. We will also do safety studies on mice of our particular algae. As we have done these studies in the past with a different inserted protein, we don’t expect many problems in passing safety tests. Algae is GRAS and people concerned with their health have been adding spirulina, chlorella, astaxanthin, fucoxanthin, and other algae-based supplements to their diet for years with no ill effects.

If all goes well with these and assorted other studies, we hope to then test on humans. First will be safety studies. As mentioned above, algae are used as a supplement by health-conscious individuals. We just have to make sure that adding the spike protein in tiny amounts, does not change the safety profile of the algae for humans.

Then we check to see if antibodies form against the portion of the spike protein that we have selected and to what extent. We can test these antibodies against a pseudo virus in a test tube to see if they kill the pseudo virus.

If we pass all of these tests, at this stage, we will have a viable candidate for an oral delivery vaccine. One of the great benefits of algae is that they double every day. And our algae have been modified to grow in fermenters. Daily doubling, plus growth in fermenters implies we should have a very economical vaccine. Most pharmaceutical companies have fermentation facilities.

We are currently searching for a pharmaceutical partner who has this capbility in addition to assisting us in testing, regulation, compliance, and distribution.

I have laid out the road map above as we try and bring an oral vaccine to market. We are currently in the process of inserting the gene into the algae after which we will do the other steps discussed above. With the assistance of RealClearHealth, I hope to bring you updates on our progress. All of us on this planet greatly desire a safe, effective vaccine. And a cheap oral vaccine would be an even greater blessing for us all.

A NOTE ON THE FLU VACCINE

Flu vaccines don’t always work and they are injections. These two attributes cause the population to use them less frequently than they would were they to be in pill form and with a high degree of efficacy.

If our algae based oral vaccine works, an obvious strategy against the common flu presents itself. Right now CDC recommends vaccinations that contain 3 or 4 flu strains. They have to choose a few because they don’t know which one will be prevalent in any given season. And their best guess can easily be wrong.

Because algae grow so quickly, the best strategy would be for us to create 20 or more different algal varieties against all of the potential flu strains. Then the CDC would wait as long as possible, gathering information from the flu season in Australia and South America. With only one month’s notice, we would distribute starter algae to all of those who had fermenters and wanted to make vaccines. In one month’s time, they could create enough doses of the correct flu vaccine for the entire country.

Daniel Gressel, Ph.D., is the Chairman of Transalgae which is located in Rehovot, Israel. He can be reached at dgressel@teleos.com.

 

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