Sharp

Dr. Stephan Sharp

Hospitals in Tennessee were delivered their first shipments of the Pfizer COVID-19 vaccine early Thursday morning and health care workers are lining up to receive their first doses. It has been nine months since the first vaccine candidate was tested in humans, and since then more than 63 clinical trials have been launched to test the various products’ safety, efficacy and long-term durability against the novel coronavirus. 

As the first vaccines begin to roll out under an Emergency Use Authorization, several clinical trials continue to test the long-term efficacy of the vaccines. Nashville-based Clinical Research Associates is currently overseeing phase-three clinical trials for the vaccine candidates developed by Pfizer-BioNTech and Oxford-AstraZeneca. With the help of some reader-submitted questions, the Post talked with Medical Director Dr. Stephan Sharp — who has been with the research firm since 1996 and overseen more than 600 clinical trials during his time there —  about the inner workings of clinical trials, what he knows about the various vaccine candidates and more. 

You can find the answers in video form at our Twitter account

Does the clinical trial prove anything except there was a response to the virus? For example, does the vaccine lessen symptoms? Give you immunity? 

The primary outcome of all of these outcomes is to look at the number of cases of COVID, comparing the number of cases in the treatment group with vaccine to the number of cases in the placebo group. If there were fewer cases in the vaccine group that means you have prevented the incidence of disease.

We are also keeping track of how many people land in a hospital due to COVID, how many died from COVID, as well as what the symptoms are. There will be people who will have symptoms and have a head cold or the flu or some other virus or bronchitis from a bacterial cause. But we will be testing people with symptoms of COVID and we will know how many are symptomatic and how bad their symptoms are. Some of the studies also look at viral shedding and how contagious they might be after getting the vaccine. We are also looking at antibody levels and other markers for the immune system's function. So we will see how well the immune response has been built up by the vaccines, and in the end, that may give us a way to tell how to predict who will respond to a vaccine without having to wait to count cases. 

So it’s measuring a whole lot of different aspects of the COVID infection.

Will people have to get vaccinated against COVID-19 seasonally, like with the flu? 

So the reason these studies have been designed to be 2-year studies is to look at what we call the “durability” of the immune response. You don’t ever know on the front-end how long a vaccine is going to keep you protected. So you measure the measurable, whether it’s antibody response or number of cases, and you follow folks long-term. We will know within a few months whether the vaccines are protective and the FDA standard is 6 months to determine the safety of the vaccine. We will then continue to follow these guys for two years to see how long that effect lasts. 

In the instance that the vaccine continues to be effective after two years, I would expect them to have what is called an extension to the study to see if it lasts three or four or five years. It took us a while to know that you need a tetanus shot every ten years. And it could take us a while how long these vaccines last if they end up lasting for several years.

Why will clinical trials for the COVID vaccines extend beyond FDA approval? 

You don’t ordinarily have these long durability trials for vaccines. It depends on how new the vaccine is. So if you are doing a new version of the flu vaccine study, you know that the flu mutates over the course of a year, so you are going to be given that vaccine every year. You have to prove that it will be safe for six months, but you’ll know your effectiveness within a few months. Some of those will go for a full year just to wear the belt and suspenders for safety data, but you are not looking at durability for let’s say you come out with a brand new vaccine, like when had the Zika vaccine or the Ebola vaccine, you have something that apparently blows up in a quick flurry of cases and doesn’t tend to last for years, so you don’t need durability that is several years long, so you are not generally looking at it then — although I’m sure there are some folks that are tracking the durability of those vaccines now. 

We know that COVID is going into other animal species, so it’s not just going to up and go away miraculously. We will be dealing with this particular virus for years to come unless it mutates to some form that no longer infects humans, but we can’t count on that. So the durability of the vaccine matters a lot because it may be something like, say, whooping cough, that you can get later in life after your vaccine durability wears off and you may need to be vaccinated on an every-few-years basis.

What are the differences between the technologies used in making the COVID vaccine candidates? 

When you are developing a vaccine, you want to know: What does the immune system recognize as foreign and what is it willing to attack? In the case of the novel coronavirus, we know that our systems will recognize what is called the “spike protein” on the surface of the virus. When we decide to use it as a target, then you come to “What is the recipe for making a vaccine?” 

One thing you can do is take the spike protein and put that in the vaccine and get the body to respond to it. The two studies we are looking at take a different path. They are taking the messenger RNA from the COVID virus, we are actually producing that synthetically in labs now, one of these vaccines packages it in little lipid nanoparticles, it’s like a fatty soap bubble that contains the mRNA. The other one used is an adenovirus, which will be like a head-cold virus, that affects chimpanzees but does not infect humans, and that acts as a carrier to get the attached COVID mRNA into cells. The lipid nanoparticles will carry it into cells. It’s two different ways of getting mRNA into our cells and our cells will then produce the spike protein in presumably greater numbers than we can deliver in a vaccine with the idea of getting a more robust immune response.

Should I expect to have symptoms from getting a COVID vaccine? What causes them? 

The idea behind using a vaccine is to provoke the immune system to respond. When you get the immune system revved up, it produces a wide array of different chemicals we call cytokines and interferons. Those chemicals actually cause symptoms such as headache and fever and chills, body aches, soreness at the site of infections, sometimes you even get a little nausea and diarrhea. All of that is due to immune response, and that is why a lot of those symptoms are similar to what you get with the infections themselves. 

The vaccine-induced reactions don’t tend to be as severe nor last as long as the infection itself. Immediately after getting the vaccine, let’s say that day or the next couple, we expect those symptoms to be due to the vaccination. If they occur later and have other symptoms attached to them like a cough or sneezing, loss of taste or smell, [those are] things we don’t typically see with a vaccine, so we suspect that is an infection and we will treat it accordingly.

Should populations not studied in clinical trials — i.e. pregnant women, individuals with autoimmune disorders, children, etc. — get the vaccine? 

That kind of goes in the “it depends” category. There are times that the studies have been a little bit overly exclusive and unnecessarily leave folks out who probably should get treated. One of the classic examples of this is that we typically exclude pregnant women from studies of drugs and vaccines and then leave it to the discretion of their physicians whether to treat them with it once it’s on the market. The irony there is most pregnant women are encouraged to get vaccinated, so there is a gap in our knowledge. 

Other groups may be studied sequentially, for instance, a drug may not be studied initially in folks who have reduced kidney or liver function but then later they’ll do a small group study of folks with those maladies to see how will the drug performs in them once they know how the drug performs in folks who are otherwise healthy. 

In this case, we have kids who aren’t currently being studies in the vaccine trials but there are being trials set up to look at pediatric dosing. Sometimes you need a different dose of the vaccine for kids than you need for adults and that is in the process now. The Pfizer study included kids down to the age of twelve, so we will have some pediatric data coming out of that trial.

What is the difference between an Emergency Use Authorization and full FDA approval for a vaccine candidate? 

So the difference between the emergency use authorization is that it’s granting — as the name says — for emergency use only a small amount of vaccine to the highest risk groups, which are the frontline health care workers and the staff and residents in long term nursing facilities and group homes. That does not mean that the vaccines have been proven safe enough or effective enough for general release. Those results will come in a few months and I’m sure the approval process will move forward at that point. But until one of those vaccines have been approved, they aren’t going to be on the market. So the only folks who are going to be getting vaccinated by the emergency use authorization will be those selected high-risk groups. 

This post originally appeared in our partner publication, the Nashville Post

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