Genetically engineering vaccines to fight COVID19 – the mRNA vaccine
With the prospect of either Moderna or Pfizer bringing their mRNA vaccine to market, I’ve had clients question me on what is this technology? In my episode on “The biggest healthcare challenge facing you today,” I talked to why it is so important to be or have a patient advocate. One of the functions which a patient advocate is able to complete is the initial research so you can start to figure out what works best for you and to allow you to have a more in-depth conversation with your medical provider.
The coronavirus is insanely risky. In the last two weeks, more and more people are comfortable talking about their infection and the lasting ramifications of the virus. Twitter is probably one of the more vocal platforms. As celebrities and influencers talk about their positive test for Covid19, more and more people are tweeting about some of the lasting health impacts of the disease. Asthma or some other impaired lung function is the most popular post I read about. But, I’m also reading about issues with brain function and dementia, post viral heart attacks, and just a slew of other things.
And pre-election, it was really hard for me to find this information. I really wanted to understand what my risk was if I survived an infection and prior to two weeks ago no one was comfortable talking about it. Nor were they posting pictures of their loved ones who had passed. The weird thing is the pictures I’m seeing are not 80 year old seniors in a healthcare facility. These people look like they are in their 40’s or 50’s, healthy and vibrant. These people were me.
But now we are going to have another decision facing us. What do we do when the vaccine becomes available? Right now, Moderna and Pfizer are leading the pack with their mRNA technology. Johnson and Johnson was working on an adenoviral vector vaccine that was pulled in the last few weeks due to an adverse incident.
So, what are these technologies? mRNA vaccine technology is one of three genetically engineered vaccine technologies. The three technologies are: 1. DNA vaccines, 2. mRNA vaccines and 3. adenoviral vector vaccines. There are over 200 hundred vaccine candidates worldwide. There are companies in each of these categories. Inovio has a DNA vaccine in clinical trials. Pfizer and Moderna have mRNA vaccines. Johnson and Johnson has an adenoviral vector vaccine.
And this is just focusing on the genetically engineered vaccines.
Let me tell you, in concept, I like the concept of genetically engineered vaccines because it takes out the variability of life in vaccines created through naturally occurring processes. And this risk really came to light back in 2009 with our flu vaccines. We’ve used chicken eggs to create the flu vaccine for over 70 years. So, it’s a stable platform with a hitch. Every vaccine would have a mutation. These mutations didn’t pose a concern because the vaccine was really about making our immune system sensitive to one protein on the virus – the only protein our immune system could target. In 2009, the mutation happened on that protein hiding it from our immune system. Back in 2019, I produced an episode on this phenomenon “Research Updates Flu Vaccine 2019.”
The episode goes over the research that was happening and some of the short term solutions of addressing the problem. Now, none of the short term solutions fixed what caused the problem in the first place. In fact, they had the potential for making that problem even worse because the problem was diversity in nature coupled with non-human DNA and injecting it into humans. I’ve been really curious how science was going to address the problem with the random nature of life. Out of the three genetically engineered vaccines, it appears that mRNA may have the potential to address this problem.
All three of the technologies have been around for 20 to 30 years. None of the technologies have an approved vaccine for human use. So, let’s look at what each of the technologies does have approved. First, DNA vaccines have two approved veterinary vaccines in the US. The West Nile Virus vaccine for horses and melanoma vaccine for dogs. Second, the mRNA technology has no approved vaccines for humans or animals. The third technology, the adenovirus vaccine has one vaccine approved for rabies in wild animals.
I would highly support reading the Chemical and Engineering article, “Adenoviral vectors are the new COVID-19 vaccine front-runners. Can they overcome their checkered past?” Well written and explains the adenoviral vaccines in clear, easy to understand language. It highlights the risks with these vaccines. It sounds like the concept is valid, but when you try to implement it, you can’t.
With the DNA vaccines, I hesitate when you inject something into our DNA. I just don’t think that is a good idea. And the West Nile virus vaccine was causing so many adverse events in horses, that I stopped using it. I stopped following this vaccine when I stopped using it. Although, I can say I don’t hear the same outrage that I heard with the initial vaccine where birth mutations were common, sudden death, reproduction concerns – just all sorts of weird DNA issues. That’s just me, and I’m sure science would be more than willing to help me understand how naive my position is.
Obviously there have been improvements in the technology. Back in 2003, there was a review on DNA vaccines. One of the problems was reaching enough cells. According to a review initiated in 2015 and finalized in 2017, that is still the problem in humans. I’ll be curious to see how Inovio is going to overcome this obstacle.
Which leaves us with mRNA vaccines. What I liked about this concept is it is synthetic. So, the risks involved in using chicken eggs to grow the virus and injecting the virus into the body are avoided. What I also like is the limited function of mRNA in the body. mRNA is a recipe or instructions our cells read to make a protein. And this vaccine is only delivering instructions to create one protein and has no other instructions. What I also like is mRNA degrades overtime so it won’t be floating around your body. It has a natural termination date.
On the other side, the biggest concern with the Pfizer mRNA vaccines is the need to keep them cold…really cold until use. That will create a logistics problem. Moderna does not need to be kept cold. That alone would make it a natural front runner over Pfizer. The other thing that is going to be tough with these vaccines is it is new technology. I know there was some concern that the data wasn’t available before the elections. There weren’t enough infections before the elections to open the data. And I still question whether 90 some infections is enough to make a determination in a population of 30,000 to 45,000 because we just don’t know what we don’t know. And that article in Chemical and Engineering news highlights what we learned about the adenovirus technology as we started trying to use it. It was identified that people who have immunity to the adenovirus used in the vaccine had no protection. In some people, this technology caused a significant inflammation response that could cause death. The researchers also found that after the first injection, the body mounts an immune response to the adenovirus vaccine. So, you couldn’t use it a second time.
So, right now, I like the concept of genetically engineered and I like the mRNA technology the most of the three available. But this is really preliminary. I thought I had read somewhere that Pfizer will open their trial data towards the end of November to allow researchers to peer into the data, but I can’t find that information anywhere. If you want to see the study design here is a link to it. https://www.pfizer.com/science/coronavirus
CNBC did a great overview of the process of getting a COVID-19 vaccine to market and mRNA vaccines called, “ What is an mRNA coronavirus vaccine.” It goes into more depth on the speed these are coming to mark, the phases of the trial, and emergency use approvals.
O.k. that is the introduction to the genetically engineered vaccines. Good-luck you guys and stay safe.
Erman, Michael Mishras, Manas (2020, October 27). Pfizer says no COVID-19 vaccine data yet, could be a week or more before it reports. Reuters. Retrieved on November 15, 2020 from https://www.reuters.com/article/us-pfizer-results-idUSKBN27C1GT
Cross, Ryan (2020, May 12). Adenoviral vectors are the new COVID-19 vaccine front-runners. Can they overcome their checkered past? Chemical & Engineering News. Retrieved on November 15 2020 from https://cen.acs.org/pharmaceuticals/vaccines/Adenoviral-vectors-new-COVID-19/98/i19
Cuffari, Benedette. (2020, September 25). What is a DNA-based vaccine?. News-Medical. Retrieved on November 15, 2020 from https://www.news-medical.net/health/What-is-a-DNA-based-vaccine.aspx.
Liu, M.A. (2003, March 21). DNA vaccines: a review. Journal of Internal Medicine. Retrieved on November 15, 2020 from https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2796.2003.01140.x
Li L, Petrovsky N. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 2016;15(3):313-329. doi:10.1586/14760584.2016.1124762
Beasley, Deena (2020, November 9). Inovio expects FDA decision on COVID-19 trial start this month. Reuters. Retrieved on November 15 2020 from https://www.reuters.com/article/us-health-coronavirus-inovio-pharma-idINKBN27P2UW