Conquering COVID Part 1.6:
“Vaccine Repurposing & now 70 potential vaccine candidates?!”
(aka the test tube Is half-full, not half-empty)
April 16, 2020
by Mark A. Moyad, MD, MPH
“I am concerned, of course, but I am also incredibly optimistic.”
Hi everyone! I want to start by giving a loud shout out/kudos to my amazing wife who has the unfortunate task of being one of my many first pass editors (along with Us TOO folks, of course) for all of these articles. Also, I want to keep thanking you, the readers, during this time. Thank you! Your comments and photos have been so inspiring, so thank you. I began writing this column today and when I simultaneously glanced out the window, snow began to fall, and I have never been so appreciative of such a unique April event. It is not as if I love snow (I have moments of like and dislike for it - just like broccoli), but I have become more hyper-sensitive of these minor occurrences in life that I have never paid much attention to in the past. Sorry, I did not intend to get philosophical right out of the gate, but I know you all know what I am trying to convey here.
First on the docket, I find it interesting when some positive preliminary research data is published on an anti-COVID-19 drug, or some other intervention, and some folks want to immediately see the glass (aka test tube) as half empty. Last week an anti-viral drug known as “Remdesivir” showed some potential benefit, but there was no control group, so it was understandable that no one is ready to do cartwheels over this data (Grein J, et al.
N Engl J Med 2020, April 10). Yet, if you want to be in my
test tubes are generally half-full
world then let me tell you why this is a nice potential first step. This drug has a broad mechanism of action, which suggests if it fails, researchers will learn to NOT target this general pathway or might focus on other more specific pathways, and researchers will also learn more about safety (not just potential efficacy pathways).
Similar to prostate cancer treatment, the pathway to better and safer treatment was also surrounded by clinical studies that “failed” but they provided a quick learning curve on how to adjust to eventually find success. Also, keep in mind that many initial anti-COVID drug studies are being tested in the most ill patients, so if ANY activity is demonstrated here, then the chances it can work earlier in the course of the disease has the potential to go up significantly.
For example, most people are either not old enough to remember, or they have forgotten, that many of the most successful drugs in prostate cancer and many other conditions were at first FDA approved for only the most advanced/ill patients and now they are almost all being utilized earlier and earlier with far greater potential success. I have NO CLUE if Remdesivir could or will be effective against COVID-19 on any level, but it has already been given to almost 2000 patients for emergency use and there are currently multiple clinical trials utilizing this drug. What I do know with certainty is that negative or positive results from these and other clinical trials will allow immediate research adjustments or learning of how to get this “darn” (sorry, again trying to exhibit decorum by not using bad words) virus. This is also how I feel about all the other interventions including: Tocilizumab or Sarilumab that target IL-6 (inflammatory marker) or the potential cytokine storm that occurs in some patients. Interestingly, to demonstrate just how interdependent research has become, and how it always provides an endless learning curve, then all you have to do is look at Actemra that was FDA approved for rheumatoid arthritis in 2010 and other medical conditions just a few years later in 2011 and 2013. In 2017 this exact same drug was also FDA approved for use to reduce severe or life-threatening “Cytokine Release Syndrome” or CRS (aka the cytokine storm), or an excessive immune reaction that could be dangerous in some cancer patients with a specific immune therapy (CAR-T). Now, as you know from reading this series of articles, this same drug is being tested right now as a way to potentially treat a similar issue occurring in patients with severe COVID-19 disease! Regardless, the point here is that there are many potential pathways to get the virus and whether the multitude of experimental drugs are effective or not, they are allowing us to narrow in on the most effective pathway for success. Okay, time to get off my EPA approved disinfected soapbox.
Just 2 WEEKS AGO I wrote a column on how there were approximately 40 vaccine candidates being tested on some level.
Well, now the count is approximately 70 vaccine candidates! This is exciting and even companies that aren’t necessarily buddies, or pals, or chums are coming together. For example, Sanofi and GSK are two very different companies, but they are similar in the sense that they are two of the more dominating global vaccine technology companies. So getting them to work together is kind of like Michigan and Ohio State football coaches sharing recruiting and other football secrets. I know, that was a weak analogy but very relevant in my little world. Regardless, this is exactly what is needed to move the ball (aka research forward)! Additionally, major league baseball teams and a variety of affiliated employees (not just the players but executives, hot dog vendors…) have in general agreed to participate in an unprecedented nationwide antibody study for COVID-19. This allows an amazing treasure trove of data to help eventually determine how to best get back into the game of life, so to speak. It will provide data that gives researchers an intensive look at the prevalence of this virus and will help expose it to better understand it’s true impact and how to mitigate it (
https://n.pr/3aeLCfv). It is probably just a matter of days or weeks before other professional and perhaps collegiate organizations also join in to contribute towards this research.
Additionally, a category of medicine that does not receive enough attention is known as
“Vaccine Repurposing” and this is happening now! I wrote in a past issue about drug repurposing, but I have not yet mentioned vaccine repurposing. What this means is that there are some vaccines that appear to provide protection or benefits beyond the medical condition or disease they are trying to prevent. For example, recent evidence suggests that the shingles vaccine may also reduce the risk of some cardiovascular disease events, such as stroke, by potentially preventing or controlling chronic “inflammation,” which could theoretically occur any time a person suffers from shingles itself (
https://newsroom.heart.org/news/shingles-vaccine-may-also-reduce-stroke-risk).
Vaccine repurposing is fascinating and should be explored as much as drug or over-the-counter product repurposing. For example, the evolving story with the tuberculosis vaccine is very interesting. It is hard for some of us to believe, but tuberculosis is still one of the leading causes of infectious disease deaths in many parts of the world (Brazier B, et al.
Semin Immunopathol 2020; March 18), and yet there has been, and still is, a tuberculosis prevention vaccine which is also known as the “BCG vaccine.” It was essentially named after some of the researchers who helped make it all happen. The BCG vaccine is given to newborns or young children millions upon millions of times a year (not in the United States). Over time research has suggested ancillary potential benefits to this vaccine including the ability to protect against some cancers and perhaps even viral infections. This is not proof, but preliminary research suggests benefits from the BCG vaccine (Usher NT, et al.
JAMA Network Open 2019 & Arts RJW, et al.
Cell Host Microbe 2018;23:89-100).
Now, here is where it gets really fascinating! Past preliminary research with the BCG vaccine has led to the immediate design and initiation of two major clinical trials in the Netherlands and in Australia of Health Care Workers receiving the BCG vaccine to potentially prevent them from being infected or seriously infected by the COVID-19 virus (BRACE trial at
https://clinicaltrials.gov/ct2/show/NCT04327206 & the BCG-CORONA trial at
https://www.clinicaltrials.gov/ct2/show/NCT04328441), These trials are immediately recruiting thousands of health care workers and now there is also a serious discussion on whether or not such a trial should be conducted in the United States. For example, hopefully at Baylor, MD Anderson, and other sites (
https://bit.ly/3cmy5nu). BCG is a live-attenuated vaccine (LAV), which means some healthcare workers will not qualify because they may be immunocompromised, and this could cause problems. Perhaps a non-LAV strain could also be tested? Regardless, if there is a hint it could protect health care workers then using it for other non-health care folks would be immediately logical, but of course I am getting way ahead of myself.
Interestingly, BCG is also well-known in the urology and oncology world, including the United States, where it has been a standard treatment of care for some types of non-muscle invasive bladder cancer (NMIBC) patients! It is placed in the bladder via a catheter (aka “intravesical treatment”) and causes an immune reaction which is extremely helpful in treating many patients with bladder cancer (Li R, Kamat AM.
Urol Clin North Am 2020;47:23-33)! In other words, the side benefits of the tuberculosis prevention vaccine and similar components utilized in bladder cancer are sufficient enough to potentially launch these clinical trials. BCG treatment is also being tested in some other cancers, but this is for a different column and a different time.
All of this stuff is so interesting and innovative and I hope it shows some activity against the virus. It is also of interest that at the time I was writing this column there was
very preliminary (still needs to be heavily peer-reviewed) evidence from researchers at the Johns Hopkins Bloomberg School of Public Health (Shet A, et al.) that deaths from COVID-19 appeared to be much lower in countries utilizing BCG vaccination for long periods of time. This does NOT prove cause and effect at all, but it is interesting and should at least encourage more population research in this area. For example, has BCG utilization for bladder cancer patients offered any protection from the COVID-19 virus and/or prevent serious infection?
Now, all of this data has brought out many negative comments of “experts” questioning this data. However, the idea of vaccine repurposing in the right situation is simply another unique pathway in ultimately providing some solution to this pandemic.
If the BCG vaccine does not work, well then researchers will immediately learn and adjust to determine other promising immunological pathways to fight this virus. What is amazing about the tuberculosis vaccine is that it was first given in 1921! Yes, 1921! So,
this track record gives me hope and hope is a valuable commodity these days. I am excited about the diversity of approaches researchers are utilizing right now in the fight against this
specific coronavirus (aka THE TEST TUBE IS HALF FULL here folks).
Thank you for reading my latest installment and I wish you and your family the best of health.
I am concerned, of course, but I am also incredibly optimistic! I look forward to modern day science and you of course, kicking COVID-19 and cancer in the gluteus maximus!
All of my best always,
Mark A. Moyad MD, MPH
Read my previous COVID-19 articles at:
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