COVID-19 Vaccine Update
We have been getting a number of comments and individuals who have expressed concerns over the speed at which the novel coronavirus vaccine is progressing. We have written about mRNA vaccines in previous posts, but we haven’t written about the variety of candidates which are in the process of development and testing.
I’m not going to lie, change and new experiences can be worrisome and scary, and I share some of those concerns. Unfortunately, whenever we have a deficit of information, it is a perfect environment for bad actors to fill that void and manipulate people with conspiracy theories and outright lies. Stress and change increase our own vulnerabilities, and this makes all of us vulnerable to misinformation as we try and bring stability to our lives. Unfortunately, we have also seen our own political leaders utilizing misinformation and disinformation for their own agendas or to gain support/power within their party/constituents.
So let’s talk about the current and potential vaccine candidates and their strengths and weaknesses. Since we don’t want individuals with concerns over one of the candidates to feel alienated and pushed towards those who want to undermine trust in science and healthcare organizations, we want to talk about the other vaccine candidates which will likely see FDA Emergency Use Authorization within the next month or so. We want to encourage those with concerns about the mRNA technology vaccines to strongly consider getting vaccinated with either of the two non-mRNA candidates which will likely be applying for FDA EUA soon. I feel like most of the concerns that I have heard expressed are focused on a few of the vaccine candidates and a review of the broader candidates will show that many have long track records of use and safety.
When we look at the Main Stream Media, I feel like we are seeing a dichotomy of different approaches to communication surrounding vaccine by the different biological companies. We had the early announcers, like Moderna, who were quick to announce and begin clinical trials for their vaccine candidates. Others delayed their announcements (like J&J’s Janssen Pharmaceuticals), which could be in part due to the timing necessary to create their initial vaccine candidate for clinical trials (mRNA vs. Recombinant platforms).
All in all, we currently have two vaccine candidates which have received Emergency Use Authorizations (EUAs) from the FDA. We could have a third and fourth vaccine EUA soon, as Johnson & Johnson and Astra Zeneca candidates have/will soon complete phase III clinical trials in the US and early results show promise (Astra Zeneca already has approval in India and the UK). It’s likely these two will seek FDA EUA in February.
Merck, Sanofi, and Novavax are three more companies which will likely start/complete Phase III trials soon. Merck, which had two candidates it was working to develop with International AIDS Vaccine Initiative (IAVI) and Themis (breakout of Pasteur Institute), has cancelled their vaccine development processes, they announced earlier today. Sanofi has three candidates, two protein vaccines with GSK and a mRNA vaccine with GSK and Translate Bio. Novavax has a synthetic protein vaccine candidate which is currently in phase III clinical trials, and could be completed at the end of March and ready for FDA review as early as April.
There are a number of other vaccine candidates which include additional candidates in the listed groups and also attenuated and inactivated vaccines, but these candidates are being tested/used predominantly outside the USA.
Major vaccine candidates based on the platform:
So let’s talk about the main candidate types, mRNA, Recombinant, and Protein/protein sub-unit vaccines.
Moderna, BioNTech (Pfizer), CanSino Biologicals, Sanofi/GSK
(Adenovirus, Measles, vesicular stomatitis [VSV]). AstraZeneca, J&J Janssen, Themis (Merck), IAVI (Merck), CanSino Biologicals, Mass General, Sputnik V,
Protein/Protein Sub Unit
Clover (Sanofi/GSK), Medicago (GSK), Novavax, Sanofi/GSK
Of all of the main candidate technologies, the novel mRNA vaccines are amazing, both in the speed in which they were able to synthesize and create the first candidate (Moderna was able to create their mRNA within 2 days of the completion of the SARS-CoV-2 genomic sequencing) and the flexibility they provide for future use. This speed can allow us to tackle other novel viruses with exceptional speed, and allow us to have an aggressive ability to control even the most aggressive pandemic with speed and accuracy.
Yet the newness and speed are also a source of fear and uncertainty. We haven’t had a successful mRNA vaccine in history, despite significant research towards cancer and HIV vaccines. mRNA has seen considerable research over the last 35 years both for targeted gene therapies, protein replacement treatments for Cystic Fibrosis and even a vaccine candidate for Zika. Throughout the last 35 years, the mRNA technology has showed no long-term harmful effects, so it is unlikely that we will see any with the novel SARS-CoV-2 vaccines.
Since the other vaccine platforms have been around for decades in other vaccines, they provide a reasonable alternative for those who have concerns about the mRNA technology. Due to the fears and concerns some have expressed with mRNA vaccines, let’s talk about the alternative recombinant and protein vaccines first.
Recombinant vaccines have been used for decades, with the introduction of the recombinant Hepatitis B vaccine in the late 1980s. The recombinant vaccines use viral vectors to introduce DNA/RNA into a medium, inducing it to produce specific viral proteins used in the vaccine. With the HepB recombinant vaccine, the medium is a brewer’s yeast. The HepB Recombinant vaccine was developed in 1987, and has seen widespread use with minimal side effects, including routine immunization of infants beginning in 1994.
With the novel Coronavirus recombinant vaccines, they are bypassing the intermediate medium and using a common virus (Adenovirus for Astra Zeneca, J&J, and Sputnik V) as a vehicle to introduce the viral RNA to produce part of the SARS-CoV-2 virus by the cell (typically the spike protein). We call this a viral-vector vaccine and is an extension of the considerable research we have with inserting DNA/RNA into cells of bacteria/fungi/plants for the purpose of excreting a specific protein. This allows the introduction of immunogenic markers of the SARS-CoV-2 virus, without exposure to the hazards of the virus itself. Adenovirus is one of the viruses which causes the common cold, so the virus is relatively harmless, so the likelihood of adverse events due to the viral-vehicle is very low. These viruses provide a low-risk platform to introduce the genetic code to build parts of the SARS-CoV-2 virus without the risk of infection.
Protein and Protein Sub-Unit Vaccines:
The protein/protein sub-unit vaccines are both new, but also not new. Most protein vaccines that have been used in the past are recombinant protein platforms or polysaccharide conjugated vaccines. We use a virus to introduce the genetic material necessary into the medium to create a viral protein, which we then purify and use in the vaccine with an adjuvant. In some of the novel protein candidates, wild tobacco plants are used to create the viral proteins (Medicago and GSK, Kentucky BioProcessing), others are using insect or bacteria/yeast to create the proteins (Sanofi/GSK). The newest technology that is seeing activity for protein/protein sub-unit vaccines are synthetic proteins, such as Novavax’s candidate. With Novavax’s candidate, they have created synthetic spike proteins and combined it with an adjuvant which causes local irritation. This activates the immune system, which then attributes the irritation to the foreign protein (the spike protein), hence initiating the immune system to further recognize the spike protein as an enemy. Sanofi/GSK has already used insects to create a flu vaccine (Flublok) which has FDA approval and is in the process of restarting phase II clinical trials with a COVID-19 vaccine based on the same approach.
Finally, let’s talk about mRNA technology, where it started, how it’s been used. We wrote earlier posts which describe the inability of mRNA vaccines to alter DNA; mRNA and concerns for fertility; why you should still get the vaccine, even if you have already had COVID-19, and concerns for pregnancy and lactation with mRNA vaccinations.
In these articles, we talk about the mechanisms by which the vaccine works, why we need specific additives in the vaccine to protect the fragile mRNA (lipids and sugars), the inability of the mRNA to migrate to other areas of the body (due to the fragile nature), and the fact that mRNA has a limited duration before it is destroyed. Since we have covered a number of the concerns with the mRNA vaccines, we will focus on the history of mRNA technology and how that it isn’t a new technology, just new to the vaccine scene. If you have other concerns, feel free to comment below or send us a Facebook/IG message or an email to email@example.com .
History of mRNA technology:
One of the earliest publications surrounding the use of RNA/DNA therapy to induce the production of a protein was in 1990. There was considerable research prior to 1990 to be able to identify how to get the DNA/RNA into the cell (phospholipid encapsulation, lipids, etc.), but this study showed that these methods could allow not only the entrance of the gene into the cell, but also the cell being able to utilize the genetic material in the production of enzymes and proteins. In this study, scientists injected the DNA/RNA genetic sequence for three different enzymes (chloramphenicol acetyltransferase, luciferase, and beta-galactosidase) and observed the mouse muscle tissue for the expression of the enzymes.
But let us take a moment and directly address a blatant piece of misinformation that is consistently shared in religious circles that mRNA technology requires luciferase to be effective. First, this is incorrect, the study showed that by introducing the genetic sequence for luciferase, the cells expressed the luciferase enzyme. Second, it is commonly said that this enzyme (luciferase) is called this due to the “devilish nature” or the “evil roots” of the technology. This is blatantly wrong, the Latin root for luciferase is referencing the luminescence that the enzyme creates which allows for bioluminescence of the tissue. This enzyme is used to create a florescent protein which does not need an external light source to be able to glow. This allows the muscle tissue to glow when the enzyme is produced, allowing the scientist to easily validate whether the genetic material was successfully introduced into the cell and whether it was allowed to produce the intended enzyme. Luciferase is the mechanism behind why fireflies, certain jelly fish, mushrooms, and other plants/animals can create glowing colors absent the present of light. This is a perfect example of how quickly and deliberately disinformation is created, acknowledging the knowledge of the lack of science understanding, knowing that the target will immediately have a visceral reaction to the word luciferase, and that the individual is unlikely to take the time to investigate the real truth behind the word. The creators of this disinformation are exploiting these biases and illustrating the need for proper education and bias self-reflection.
Very quickly after it was shown that we could use DNA/RNA to produce proteins, we have a study which showed that we could introduce the genetic sequence for Desmopressin (anti-diuretic hormone, a complex human hormone) into rats and the rat’s cells would secrete Desmopressin. This could reverse Diabetes Insipidus, a disease which caused by a lack of Desmopressin. This showed that the introduction of DNA/RNA wasn’t limited to an enzyme, but complex proteins (and larger genetic code profiles) could be utilized.
Through the next thirty years, we have seen research into anti-cancer vaccines, personalized vaccines for specific antigen receptor targeting, allergy therapy, genetic disease therapy, and countless more areas. There was considerable research into how to be able to get the mRNA to be stable enough to consistently enter the cell and produce a consistent output, dosing of the mRNA, etcetera and this was all before SARS-CoV-2 even presented on the scene. We have seen attempts at utilizing mRNA technology for Zika, influenza, and a few other infectious diseases, but the funding for large studies didn’t exist, as we already have cheap and stable platforms for these diseases or the disease itself only affected limited number of individuals. Once SARS-CoV-2 came onto the scene, there was an impetus to rapidly create a vaccine for this new infectious disease, and to do it at an incredible pace. Since we had the research from both SARS and MERS, two similar coronaviruses, we were able to quickly pick the spike protein as the most probable candidate for vaccines.
The major limiting factor with mRNA technology (as with any novel technology) is the inherent limitations with funding. This funding often comes from a mixture of sources, including private foundations, pharmaceutical companies, and governmental agencies. This allows for a variety of different technologies to be funded (often including unproven technology funded through the government, so the government absorbs the risk). Much of this research is completed either in higher education laboratories or by private company’s R&D labs.
Since COVID-19 was recognized as a significant threat to our civilization early on (despite what politicians have claimed), actions always speak louder than words. Billions of funding have been committed and spent on research and productions of vaccines for the novel SARS-CoV-2 virus. With this funding and the impetus of the emerging threat of COVID-19, pharmaceutical/research companies had the funding to be able to perfect and implement mRNA technology in vaccines. Without this funding, it is unlikely that Moderna would have been able to test their vaccine candidate or produce it at any level. Pfizer has the resources to develop and test, without federal funding, which is why they declined Operation Warp Speed funding for the initial development and instead contracted with the US government for millions of doses of their mRNA vaccine.
So this is a summary of the major vaccines which are either under EUA or may soon be available for use on the US. Feel free to comment with questions, send us a message, or email us at firstname.lastname@example.org