Jean Patterson, PhD, on the COVID-19 Vaccine, mRNA Vaccines
In this podcast, Jean Patterson, PhD, discusses mRNA vaccines, COVID-19 vaccination, and the trials that led to the vaccines' approval for emergency use.
- Resources: Vaccination Planning. American College of Physicians. Updated January 4, 2021. Accessed January 8, 2021. https://assets.acponline.org/coronavirus/scormcontent/?&_ga=2.59967405.1227884443.1608736866-1332072176.1608736866#/lessons/kwJbUTKXK1SULXbRPFsZbpMAMKMMXgV9
- Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States. Centers for Disease Control and Prevention. Updated January 6, 2021. Accessed January 8, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
- Interim Considerations: Preparing for the Potential Management of Anaphylaxis After COVID-19 Vaccination. Centers for Disease Control and Prevention. Reviewed December 31, 2021. Accessed January 8, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html
For more content from our partners at Texas Biomedical Research Institute, visit the website.
Jean L. Patterson, PhD, is professor at the Texas Biomedical Research Institute in San Antonio, Texas.
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Amanda Balbi: Hello everyone, and thank you for joining us on Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360 Specialty Network.
COVID-19 vaccination has begun to roll out in the United States. Two vaccines are currently approved for emergency use, with other vaccines in the pipeline.
With us today to share her knowledge of the vaccines and the trials leading up to the approval of emergency use is Dr Jean Patterson, who is a professor at Texas Biomedical Research Institute in San Antonio, Texas.
Thank you for joining me today, Dr Patterson. To start, what COVID-19 vaccines are currently in the works? (at Texas BioMed or more generally)
Jean Patterson: Well, we have done some work with Novavax. Their vaccine is bacillivirus-expressed protein particles. That one, I not sure where it is in clinical trials, but a lot of the preclinical work on animals was done at Texas Biomed.
We also worked heavily with Johnson and Johnson on their Ebola vaccine, which I believe was approved in Europe at least. That's an adenovirus-based platform. Johnson and Johnson and a subsidiary, Janssen, are also using that adenovirus platform to make a COVID-19 vaccine, although we haven't been involved in that preclinical trial.
Mostly, we've been involved with developing the animal models to make available to companies. Also, one of our investigators, Ricardo Carrion, has been heavily involved with Regeneron’s monoclonal antibody cocktail, where we did the major preclinical trial in monkeys. He's also been involved with working with the Regeneron when they developed the same kind of cocktail for Ebola virus.
Amanda Balbi: And so what are mRNA vaccines, and how are they different from the vaccines we already have?
Jean Patterson: That's a new major platform for development of vaccines. It's been looked at for somewhere between 5 and 10 years now, where people have been looking at the basic science behind directly adding messenger RNA into cells and having them come back and translate the protein and express the protein.
There was an earlier technology with DNA vaccines that never actually got to approval stage, although some are clearly far along to be approved. That was a little bit more problematic, because we weren't exactly sure how this DNA platform worked, the entire mechanism. But mRNA is very clear. It gets into the cytoplasm and presumably translates the protein through normal ribosomal machinery.
It is actually a new paradigm, if you think about it, for developing vaccines for new and emerging diseases. As soon as you know the sequence of the virus, which we can do now in hours, if we can isolate the virus or for that matter other pathogens, you know immediately if it's in a family of viruses that we've seen before. We know pretty much what the major dominant epitope is and what protein that comes from. It's almost always the major surface protein.
So, we can synthesize that RNA, again, within hours of learning what the virus is, what the sequence of that particular viruses, and then synthesizing the messenger RNA. There is talk where we could actually have a lot of these stockpiled in various stages of development as these viruses emerge. I believe that this will be the platform that will be used from now on, as something as serious and as quickly emerges as COVID-19.
In any case, the 2 companies that are furthest along in this, obviously, are Moderna and Pfizer. The way they were each formulated was slightly different based on the liquid formulations. I mean, I'm not an expert in this, but apparently that's what leads to the need for different temperatures.
Pfizer seems to require a very super cold environment. Moderna doesn't need or require as cold, but mRNA viruses cannot be transferred in room temperature, say, as a DNA virus, which was one of the advantages of DNA virus. It's very stable.
Again, those the way these were synthesized, identified, and started in clinical trials is the reason that it went so quickly. The adenoviruses are Johnson and Johnson, again, which developed the adeno platform for both the Ebola and zika. Then AstraZeneca, which had been working on a vaccine for MERS, I believe, and so they had already tested their adenovirus vector with MERS, which is another form of coronavirus.
Amanda Balbi: When it comes to clinical trials, typically how long should the trial period be in order to observe any adverse outcomes?
Jean Patterson: That's an excellent question but a tricky question. I mean, in the past, the fastest we’ve ever developed a vaccine through the normal clinical trials was mumps, and that took about 4 years. Clearly, there wasn't the kind of fatality rate would mumps, which would encourage us to try to speed up the process.
There were ways that that process was sped up, and I have to admit, it was clever and safe. One of the reasons that it was able to be sped up is that the government or other entities put in all the money necessary right away. Often when a company is developing a vaccine, they go one step at a time.
They look at how well does it work, and can we synthesize it well? How well does it work in rodent animal models? Then, how well does it work in nonhuman primate models, if there's one available? This is all done because there's financial risk at each stage. If it fails at one stage, you don't want to put money into a clinical trial if it's already it's failed at an early stage. By prepaying for everything in advance on the assumption it was all going to work, the companies could do things in parallel, like they did the animal studies in parallel—rodents and nonhuman primates. They also did animal studies in parallel with starting phase 1 safety studies.
Phase 1 is the safety's trial, which is done with healthy young adults usually. These are usually volunteers. Phase 2 is done, again, testing the safety but with different demographics—older, younger, some with morbidities. Then they look at some efficacy at phase 2. Phase 3 is all efficacy. Use a larger number of volunteers, and you look for any adverse reactions and for true efficacy. Are the people that are getting vaccinated less likely to have disease than the people that are receiving placebo?
Now, there were a lot of reasons why this was easier to look at than previously. One, there was a rolling review of data as the data came out, instead of—most companies like to put all of their data together in a very complete package worth going over intensely over and over again at once at the end of everything. What the government and the FDA allowed was to provide a rolling review of data. So, as data was coming out, it was allowed to be evaluated by the FDA.
There was also a lot of social media used to find volunteers. In the past, it hasn’t that easy to find volunteers. I mean, you have to advertise, you have to go out and recruit. Because of the social media we have available today, people could be notified that there was a trial in their area and that you could apply to be in it.
And then of course there was also remote monitoring. Because we're in the middle of the pandemic at the same time we're trying to make the vaccine, you don't want to put those volunteers more at risk for acquiring a disease. In general, you would have volunteers who are taking the vaccine come back and forth to be examined. They did a lot of remote monitoring of disease, which prevented them from having to become back into clinics where they could be more likely to catch the disease. And then, ultimately, they did phase 2 and phase 3 at the same time, again with careful monitoring of side effects and adverse reactions.
The result was that we were able to do this quite quickly compared with previous attempts of vaccine development.
All of the platforms that were being done in this way—adeno, mRNA, bacillovirus-expressed proteins—had all actually been previously tested for safety. So, we knew that when we were looking at other diseases with mRNA previously, although none of them had been approved, they'd already shown that it was safe to give to humans.
And also adenovirus had been tested in many, many arenas, and it was known to be a relatively safe, as well as the bacillovirus-expressed proteins. So, these platforms have been in the works, building on the safety data. So, it wasn't just the data that was available from using it for coronavirus, but it was safety data that have been developed as we've been trying to use it to develop vaccine for other pathogens.
And many of these companies had already been working with their platform on other coronaviruses, like AstraZeneca had MERS, SARS, and some companies were underway with coronavirus as a common cold. It wasn't just the data that was available on this particular pathogen. It was an accumulation of safety data, efficacy data that have been acquired through a good 10 years or more of looking at these platforms.
Amanda Balbi: In your opinion, were the trial periods for the Pfizer and Moderna vaccines long enough?
Jean Patterson: I think they were. I think that there was so much historical data on these platforms. There was so much data being developed quickly, and the data was being analyzed constantly. So, I think, while it feels rushed, it really wasn't.
As we can see, there were so few adverse reactions, with the exception of maybe these allergic reactions, which were few and far between. I think that it was done appropriately and with the amount of care you would need to make a safe vaccine.
Amanda Balbi: What is your opinion about the adverse outcomes around the current COVID-19 vaccine and its reaction with series allergies?
Jean Patterson: Well, it's obviously a concern. Again, I don't know more than what I read in the newspaper, but both these 2 people in the UK already carried EpiPens with them, which meant they were at risk for anaphylactic shock for some other allergen. Maybe it's shellfish. Maybe it's cats. Any variety of things can cause anaphylactic shock. But for someone who's prone to anaphylaxis, it's a different set of morbidity, and it's one that you have to be very careful with.
My understanding is that anyone getting the shot now is required to stick around for at least 15 minutes and anyone who has had a serious allergic reaction is required to stay around for 30 minutes. The reason you carry an EpiPen is that it can be administered immediately, and it's very effective at blocking an anaphylactic reaction. Most people give it to themselves if they feel the reaction coming on.
And so, I think that this was not unanticipated. It certainly was expected. And we see it with almost all vaccines.
Amanda Balbi: Do you think the vaccine would reduce the transmission of COVID-19 or prevent serious illness?
Jean Patterson: When the clinicians were monitoring the effects of the vaccine, what they were looking for was disease. Again, they didn’t want to do it with people coming into the clinic. They did it by a lot of remote monitoring and reports. So, they asked, “Have you had a fever today? Have you had a runny nose? Have you had chills? Have you had breathing difficulties?” And so, the read-out for the efficacy of this vaccine was “Are people showing symptoms?”
The read-out was not “Have you been blocked from getting infected?” That take a lot more laboratory work and would’ve required a lot more time, when in fact, with all diseases, we don’t care about the virus; we care about the disease. So, the vaccine was being monitored and the read-out was to determine whether the vaccine is preventing disease.
But it doesn’t say is whether it was sterile immunity. These people had absolutely no viral infection. Sterile immunity is difficult to get, even in the best of vaccines. That’s something that needs to be looked at very carefully to prove that you’ve completely blocked infection.
So, now the question is, “Does it block transmission? Can you still transmit it? Did you get a small amount of virus, but your immune system was able to kick in fast enough that you prevented disease, but were you still able to spread it?” And that we don’t know.
That will be determined relatively soon as people start looking at these people to see if people in their households get sick. Now they’ll probably do a subset to see if people are actively shedding virus after the vaccine. That takes a lot of time and actually puts the volunteers more at risk.
So, the best thing to do is just find out whether these vaccines prevent what we’re concerned about. What we’re concerned about is people getting very sick. That’s what they look for, and that’s what they determined the vaccines were proven to be effective against.
Again, the speed with which this was done, I think it was done with this in mind: the faster we do the trial, the more likely we're going to save lives. And while these people were being vaccinated in the trials, they were saving lives. Clearly, the vaccine was saving lives. So, this was a monumental task. It's a moonshot, and we're just fortunate that there's been so much basic science funded and developed in this country that allowed us to step in and make this happen.
Amanda Balbi: Thank you so much for joining me today and answering all my questions.
Jean Patterson: Well, you're very welcome. Thanks for having me and I hope that I provided some important information and that people will get ready to take the vaccine.