Here’s Your Behind The Scenes Look At A Vaccine Trial

Infectious Disease Specialist Answers Our FAQs About COVID-19 Vaccine Trials

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Scary Mommy and SILVIO AVILA/AFP/Getty

The possibility of a COVID-19 vaccine has been discussed since the moment the World Health Organization (the WHO) declared the novel coronavirus a global pandemic. News about vaccine trials phases and successes and struggles has been making headlines for seven months. Which means the idea that a vaccine might be the key to get us out of these unprecedented times and back into precedented times has been buoying my hopes since the early days of March.

But many of us, probably most of us, don’t really understand the process of testing a vaccine. What does a vaccine trial mean? What’s the difference between Phase 1, 2, or 3? And, most importantly, when can we expect a vaccine, and will it be safe?

Scary Mommy spoke with Dr. Sharon Nachman, MD, Chief of the Division of Pediatric Infectious Diseases at Stony Brook Children’s Hospital, to get a behind the scenes look at the processes that go into creating a safe and effective vaccine, as well as what a COVID-19 vaccine might mean for purposes of herd immunity and returning back to normal.

For any vaccine or therapy, there are three phases to a trial.

The purpose of phase 1 in vaccine trials is to determine the right dose to administer. Trial administrators are searching for the dose that will create an immune response that is not too minimal and also not too extreme. In this phase, generally, a small number of healthy adults are recruited.

Once the trial administrators have a sense of the appropriate dosage, phase 2 can begin. In phase 2, experts compare one or two of the best doses and look for safety signals, or the side effects. In many cases, between 20 and 50 people may be recruited, or up to 100.

The problem with using such a small sample size may be that some side effects are missed because they occur in 1 out of 1000 cases, and with only 50 or 100 patients, the likelihood is high that the side effect wouldn’t appear. In that case, researchers might believe there isn’t a side effect.

Which is where phase 3 rolls in. Once researchers know the appropriate dose and have some idea of the side effects, the trial can begin to enroll more people and compare the safety and efficacy of a vaccine against a placebo.

All trials do have limits, and may not catch every potential safety signal. “Different phases let us understand more about the vaccine, but not everything. We could have a safety signal in 1 out of one million patients, and we would need enrollment of 2 million to find that,” says Dr. Nachman.

The challenges to vaccine developers with respect to COVID-19 are asymptomatic infections and the fact that this is a completely novel virus.

Here’s Your Behind The Scenes Look At A Vaccine Trial
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When it comes to a COVID-19 vaccine, developers are looking at two different measures of success. One measure may be whether the vaccine prevented severe illness that resulted in hospitalization. Another measure may be whether the vaccine prevented infection at all. Developers will have to parse out whether the vaccine prevented asymptomatic infections—which are contagious and contribute to spread—or not.

When it comes to the novelty of the virus, we do not yet know whether the antibody made (whether made due to infection or vaccination) will be useful in a year. Dr. Nachman notes that we don’t know the dynamics of how quickly a COVID-19 antibody fades and how quickly the body, when it sees an infection again, will remember and respond.

Herd immunity may only be reached by widespread vaccination.

Herd immunity requires that 80% of the population is immune to the virus, according to Dr. Nachman. She notes that it’s not clear at this point whether herd immunity is even possible through infection, as we’ve already seen people who’ve been infected a second time. She notes that a vaccine antibody response is different than an infection antibody response in ways that might be crucial to achieving herd immunity.

“When you get a vaccine, you make a targeted, better antibody response and your body remembers better,” than if you’d created antibodies due to an infection, she says, and notes further that vaccine responses are generally more robust and last longer.

The speed at which the COVID-19 vaccine trials are progressing isn’t alarming.

Early in the pandemic, any optimistic discussion of a quick rollout of a vaccine was tempered with reminders that vaccines take years to be developed, tested, produced, and distributed. And yet, we may see a vaccine before the end of the year. This has many worried about the safety of the vaccine.

When Scary Mommy posed the question to Dr. Nachman, she wasn’t concerned by the seemingly speedy timeline, and noted that the speed with which vaccines are progressing through trials isn’t surprising. For one, the entire genetic sequence of the COVID-19 virus was published in January and everyone began looking into the virus. Whereas in most cases viruses have a certain small portion of researchers paying attention, COVID-19 brought together all of the brightest minds across the globe.

Secondly, she notes that with respect to COVID-19, researchers had a significant jump start and as a result are starting way ahead of where usual production would begin. Many of the background pieces already existed. Companies working on these vaccines are building on current platforms of successful vaccinations and using lessons learned during Ebola, SARS, and other outbreaks.

Even once a vaccine is developed, it will take time before it reaches the public.

Here’s Your Behind The Scenes Look At A Vaccine Trial
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A multitude of steps need to happen before a vaccine reaches the U.S. public. First, a phase 3 clinical trial has to be reviewed by a conflict-free, unbiased Data Safety Monitoring Board. Once reviewed and approved by the board, it must be reviewed by the FDA. As part of that process, the FDA hosts an open forum that allows for public comment. After that, the FDA votes to approve the vaccine or not. If approved, the vaccine is turned over to the Advisory Council for Immunization practice (ACIP). Their job is to decide what age groups and which populations in those age groups the vaccine is best for.

Other, more administrative, details need to be ironed out before the first vaccines can arrive at your local pharmacy, as well. Everything from storage concerns—whether the vaccine requires special refrigeration or freezer conditions—to administration issues need to be considered.

Additionally, there’s a good chance that we will have more than one vaccine available. Pharmacies and health care professionals will need a tracking system to keep records of who received what vaccine, particularly if a booster shot is needed. A patient cannot receive a vaccine from one company and a booster from another.

Trials for children are just beginning and are an important step in achieving herd immunity.

Vaccinating kids needs to be part of a herd immunity idea because unless children are immune to the virus we can “never shut the faucet off,” according to Dr. Nachman.

While vaccine trials in children may seem intimidating, the process for vaccine trials in children mimics the process used for adult vaccine. One difference, Dr. Nachman notes, is that developers are less comfortable giving half the children in a study a placebo and waiting to see whether infection occurs. Instead, developers may use a surrogate marker and measure antibody levels to determine whether a child has some level of immunity.

Many vaccine candidates are not using live viruses.

Pfizer and many other similar companies are not using live virus in their vaccine candidates. This means that, though there may be pain at the site of injection and even a slight fever in some cases, the coronavirus is not replicating in your body. Any symptoms resulting from injection are not due to coronavirus infection induced by the vaccination, and the person is not contagious.

The world is waiting with bated breath for a vaccine, and chances are, we’re close. In the meantime, the more we all know and understand about the vaccine and the process it went through to reach us, the better prepared we’ll be for whatever comes next.