Should you get the COVID-19 Vaccine when it's first available?

Posted by Craig Wesley on

Spoiler: if it's an mRNA vaccine from Moderna or Pfizer, then be sure to make an informed decision. Don't take the decision lightly. If it's an adenovirus vector from Johnson & Johnson or AstraZeneca, then it's very slightly more proven than mRNA, but it's still not an easy decision. If it's a measles vector or recombinant vesicular stomatitis virus (rVSV) technology vaccine from Merck, then you can feel a lot more confident about its safety. Last, but not least, if it's Glaxosmithkline (GSK) & Sanofi Pasteur's combination of their recombinant protein technology and pandemic adjuvent technology, then you can also feel more confident about its safety. In the end, they all have to be proven safe through a phase 3 clinical trial and even then I'd still want to wait and see for some of these technologies.

A recent poll by USA Today/Suffolk showed that two-thirds of USA voters would not take a vaccine when first available, with a quarter saying they plan on never getting it. As I was writing this post, a group of nine pharmaceuticals, including Merck, Pfizer, GlaxoSmithKline, and biotech firms pledged not to release a vaccine until after phase three trials have proven efficacy and safety to help instill public confidence.

Unfortunately, in my opinion, that pledge is a bit of smoke and mirrors, at least by some of the pharmaceuticals. Pfizer CEO, Albert Bourla, while going along with this pledge, says they will have "an answer" by October and went on to say that people who don't take the vaccine will be the "weak link" in the chain. And don't be mistaken, he means the Pfizer COVID-19 vaccine because that is the most likely to be first approved by the FDA under an emergency use authorization.

I mention this below, but the Pfizer vaccine is an mRNA vaccine. An mRNA vaccine has never been approved by the FDA for commercial use and trails for Pfizer's COVID-19 vaccine only started on April 29, 2020. October 2020 is obviously less than a full year to know about its safety. For me, there is some cause for concern. While mRNA is said to be a promising technology, Dr Laura Blackburn, Head of Science at the phgfoundation, wrote, "we need a better understanding of their potential side effects, and more evidence of their long term efficacy." This was first written in October 2018 and is still on the foundations website because I believe it still holds true.

Update: Pfizer CEO, Albert Bourla, says that their vaccine could be given to Americans before the end of 2020, less than one year since starting clinical trials. In my opinion, he is publicly priming people to get ready to take the Pfizer vaccine, especially following the "weak link" comment he previously made about those not wanting to take a vaccine.

To be honest, I'm in the two-thirds who are not willing to take a vaccine when it first comes out, especially if its approved in 2020 or even early 2021. I know the other one-third is probably thinking to themselves, "it's because of people like you that we'll never get out of this situation." In my defense, I can count on two hands the number of times I've left the house since the San Francisco Bay Area first initiated the shelter-in-place order on April 7, 2020 and almost all those trips were for doctor appointments for my wife and my mom, combined with a total of four trips just dropping off mail at the box. All essential goods are delivered to our house using Amazon, Instacart, and other third-party services.

Yep, that's it and I don't plan on letting my guard down until there is a vaccine available. The reason being that our household includes my wife, our unborn baby, and my 69 year old asthmatic mother. We're a multi-generational household, not a house full of healthy 20 or 30 years old. COVID-19 could prove extremely disastrous for our household.

But, the reason we haven't moved to a remote location far from people and essentially lead a mostly normal life is because I do believe a vaccine will come. I'm just not planning on taking it until I've seen the data. And that's the key, the data from the clinical trials.

For myself, I will not take a COVID-19 vaccine when first approved, especially if it's in 2020 or early 2021, because I'm worried about serious adverse events (SAE). The U.S. Food & Drug Administration defines SAE as "An adverse event is any undesirable experience associated with the use of a medical product in a patient." This includes death, permanent damage, birth defect, hospitalization, and more. I'm sure I'm not alone when I say this is my main concern about taking a COVID-19 vaccine.

Trust in the FDA is rightfully shaky, nonetheless I do have relative faith in the data provided by the clinical trials. For example, Moderna's Phase 3 trial will include 30,000 participants (half will get the "real" vaccine), which is fairly large, and trial sites include such institutions as Kaiser Permanente - Seattle, UCLA Vine Street Clinic, University of California at San Diego, and University of Texas just to name a few. If for some reason Moderna, or even the FDA, tries to fudge any data, then the chances of a whistle blower coming forward is extremely likely.

Additionally, Moderna will follow participants 759 days (2 years) after the second dose to record "Adverse Effects" and "Medically Attended Adverse Effects." 759 days is an extremely long time when comparing it to an influenza vaccine. For example, the original version of Fluarix, which is the flu vaccine Kaiser Permanente administers, was approved with only 2,000 participants and followed participants for only 21 days for adverse events. The first clinical study started in May 2002 and FDA approval was granted in 2005. Of course, the big difference is that flu vaccines were first studied in the US in the 1930s. For the seven known human coronaviruses there is no FDA approved vaccine.

Even though Moderna is believed to be one of the front runners for a COVID-19 vaccine, the phase 3 clinical trial will not be finished within 2020 or even 2021. It's estimated primary and final completion date is October 27, 2022. But, it doesn't mean there will not be an approval through an "emergency use authorization." And that's unfortunately where the problem stems from.

If Moderna shows an efficacy of at least 50% (the flu vaccine is about 60% effective), then the FDA will mostly likely grant emergency use authorization. While the efficacy data should be mostly reliable, the data for adverse effects/events will not be.

I believe the reason Moderna is using a 759 day trial period is because an mRNA vaccine has never been approved. So, unlike more recent flu vaccine that follow up on adverse events between 21 days and in few cases up to 1 year, mRNA requires more data on adverse effects because it is so new. One of the biggest fears is that a mRNA vaccine platform can cause inflammation or autoimmune reactions.

So those rushing into the mRNA COVID-9 vaccines by Moderna or Pfizer should make a very educated decision on whether or not they want to be one of the first people in the world to widely test this technology. It's not like your trying out a pair of Google Glasses or getting the newest Apple product.

I personally don't know if I'd feel safe taking an mRNA vaccine within the next five years, let alone the next year or so. Fortunately, mRNA vaccines are not the only ones in the pipeline.

The next group are adenovirus vector vaccines, which is the technology being used for the Johnson & Johnson, AstraZenica/Oxford, and the "Russian" vaccine. Once again, there are no commercially approved FDA Vaccines for humans. While Russia approved their Sputnik V(accine), it is not approved by the FDA. Apparently, there is one commercial rabies vaccine for wild animals.

Adenovirus Vector Vaccines have previously been in or are currently in clinical trials for Ebola, HIV, and Zika Virus by Johnson & Johnson. One HIV study had 2,500 participants, half receiving the real vaccine, and showed to have "acceptable" side effect. Oddly enough, six people did die during the trial, but they all belonged to the placebo group, with such causes as multiple stab wounds, suicide, drug intoxication, acute pancreatitis, and myocardial infarction. I guess  the vaccine was safer than living life. China also approved an emergency use vaccine for the Ebola using the technology. Additionally, an extremely small safety trial of 48 participants is currently in Phase 1 trails for a MERS vaccine by the University of Oxford, who is working on the AstraZenica vaccine.

Update: AstraZenica halted it's trail for a little under a week when one of the trial participant, who did receive the live vaccine, developed symptoms consistent with transverse myelitis, a rare inflammation of the spinal cord.

In many ways, Adenovirus Vector Vaccines have a head start compared to mRNA vaccines in terms of data, but nonetheless there are no commercially available FDA approved vaccines for humans. I would feel more comfortable taking a Adenovirus Vector Vaccine over an mRNA vaccine, but it all comes down to what the data says and waiting for the completion of the phase 3 trials. Unlike the rest of the vaccine vectors/technologies being used by Merck and GSK, the adenovirus vector vaccine is still relatively unproven.

Last, but certainly not least, are the vaccines that Merck and GSK are working on. Merck, which is taking it very slow in the COVID-19 vaccine race, has two vaccine platforms, one based on a measles vector and one based on the recombinant vesicular stomatitis virus (rVSV) technology, which is used in the first FDA approved Embola virus vaccine for humans. While rVSV technology was just approved in December of 2019 by the FDA, it's still one more than mRNA or adenovirus vector vaccines, at least in regards to humans, and was in clinical trials for about 5 years. The measles vector is a modification of the measles vaccine Schwarz strain, a childhood vaccine used since the 1960s. In a way, it's a proven, yet still unproven, vector technology since it's taking the the safe and proven attenuated measles virus, but still modifying it vaccinate against other viruses.

GSK, working with Sanofi Pasteur, are attempting to combine two FDA approved technologies. They will attempt to use Sanofi's recombinant protein-based technology, which is currently used in their FDA approved influenza Flublok vaccine, and combine that with GSK fairly established pandemic adjuvant technology. Flublok was first approved by the FDA in 2013, so there is definitely some track record for their recombinant technology and its safety.

Everything being equal, for example if all were available at the same exact time, had the same efficacy, and all said were "acceptably safe," I would most likely want to take the GSK/Sanofi vaccine. Sanofi's Flubok has been approved since 2013 so their recombinant technology has a longer track record that just about everything else mentioned. Then I would strongly consider Mercks two offerings and, with a decent amount of hesitation, an Adenovirus Vector Vaccine. I would probably skip an mRNA vaccine and wait it out for a more proven technology to be approved.

Unfortunately, everything isn't equal and so what will be most important is to look at the clinical trial data for whatever vaccine is eventually approved. A clinical trial just started in Brazil using China based SinoVac's vaccine, which using a chemically inactivated version of COVID-19, which is considered an old fashioned technology. It the same technology used in Hepatitis A, Flu, Polio, and Rabies vaccines. That could end up being the safest and effective of all the vaccines for all we know at the moment.

I'll repeat myself again, in the end, it'll come down to what data is reported in the phase 3 clinical trials. Even then, some people may want to wait because not all trials are created equally. For example, Moderna's phase 3 is estimated to complete primary trials by Oct 2022, while Pfizer estimates it'll end it's primary trials by April 19, 2021. It's very realistic that Pfizer will "complete" phase 3 trials by that date, even though final completion is estimated to end in November 2022. The FDA will probably try and convince everyone that they know all Serious Adverse Events, including prolonged events, literally within a year of starting that trial. Like I said, not all trials are created equal. As you can guess, I personally wouldn't take Pfizer's RNA vaccine until November 2022 or possibly beyond, and only if no other vaccine is available.

For those of you who know for sure you're going to take the first FDA approved vaccine, very possibly through emergency use authorization, you essentially should consider yourself as part of the clinical trial. The big difference is that adverse events will not be included in the trial data, but rather you or your doctor should, as a community service, report them through the Vaccine Adverse Event Reporting System (VERS). This will go a long way to see if these vaccines are truly safe for everyone else.

Finally, I will mention that this puts Russia's vaccine approval into perspective. Essentially, they're extending clinical trials into an uncontrolled public trial. That's essentially what they're doing and the Trump Administration, and it seems like the FDA, are not far behind that rational.

Putin approved their vaccine on August 11, 2020, while Trump is pushing for a vaccine approval by November 2020, only 4 months difference. People were outraged that Putin and Russia would do such a thing, but Fauci says it's possible to have our vaccine ready by the end of this year, 5 whole months longer. I guess those five months makes us look more legitimate. On a side note, Merck's CEO is not rushing anything because he doesn't see how any effective and safe vaccine would be ready in such a short time, which is another reason why I would take a Merck vaccine over one that looks certainly rushed for approval.

Ironically, the vaccines using the least proven technologies will most likely be approved first, while those using more proven technology will probably be last. Definitely try to remember point when it finally comes time to choose a COVID-19 vaccine. Of course, that's if we're lucky and have several vaccines to choose from.

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