FYI: Human trials for vaccines are just one part of a very long process.

By Claire Gillespie
May 15, 2020
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COVID-19 has been wreaking havoc on the globe since it was first discovered in China in December 2019, and that's largely due to the newness of the illness—no one was immune to SARS-CoV-2, the virus that causes COVID-19, and we didn't (and still don't) have a vaccine that to protect people from it. That's why scientists have been working around the clock to develop a coronavirus vaccine—and now, just a few months into the fight against COVID-19, those scientists have begun testing the potential vaccines in clinical trials.

On May 5, two large pharmaceutical companies—US-based Pfizer and Germany-based BioNTech—began human trials in the US for potential coronavirus vaccines they developed together. Just two days later, Moderna Therapeutics, a Massachusetts-based biotech company, announced the start of their own FDA-approved clinical trial for a potential vaccine. And Pennsylvania-based Inovio Pharmaceuticals, which started developing their COVID-19 vaccine in January, announced on May 12 that it expected “to have preliminary safety and immunogenicity data by late June.”

Of course, that's not all; according to MarketWatch, at least 10 different US companies are currently in preclinical or clinical trials for a coronavirus vaccine—and worldwide, The New York Times reports that 70 to 100 companies, groups, and academic institutions are working on coronavirus vaccines.

The amount of manpower behind the search for a vaccine is clearly good news—vaccines are considered to be the most effective weapons to protect people from infectious disease threats—but the development cycle for a new vaccine is a lengthy, complicated process. Here's what you need to know about what's going on right now with coronavirus vaccine clinical trials—and why we're still likely a ways away from one being available to the public.

What exactly goes into developing a vaccine?

Developing a vaccine in a multi-step process, from the initial, exploratory stage through to manufacturing and quality control. And the clinical part of developing a vaccine, during which the human trials take place, has three phases, per the Centers for Disease Control and Prevention (CDC):

  • Phase 1: Small groups of people receive the trial vaccine.
  • Phase 2: The clinical study is expanded and more people—specifically people similar to those for whom the vaccine is being developed—receive it.
  • Phase 3: The vaccine is given to thousands of people and tested for efficacy and safety.

Regarding a few of the current coronavirus vaccines in particular, “the objective of the first stage of Pfizer and BioNTech’s Phase 1/2 trial is to assess the safety, tolerability, and immunogenicity (the ability to provoke an immune response) of our four vaccine candidates,” Kathrin Jansen, PhD, senior vice president and head of vaccine research and development at Pfizer, tells Health. “We will then select the optimal candidate and dose level for further study in a larger number of people.”

Jeff Richardson, a spokesman for Inovio, tells Health that they have enrolled all 40 participants in their Phase 1 human trial and will then move into Phase 2/3 testing as soon as the preliminary data is available. Some phases are combined to accelerate the process, Richardson explains (think: Phase 1/2 and Phase 2/3)—that's because time is of the essence when it comes to a highly infectious virus that has caused a global pandemic. 

What's being tested during these COVID-19 vaccine trials? 

This is where things get really complicated. “There are several different vaccine trials going on around the world; each is using a different vaccine candidate,” Amesh A. Adalja, MD, an infectious disease experts and senior scholar at the Johns Hopkins Center for Health Security in Maryland, tells Health

Pfizer/BioNTech and Moderna, for example, are currently testing mRNA (messenger ribonucleic acids) vaccine candidates. According to Pfizer, these mRNA vaccines don't need the actual virus—in this case, SARS-CoV-2—to be built, and instead, only rely on knowing the genetic sequence of the virus. This mRNA is a synthetic version of what a virus uses to build infectious proteins, and when it enters a cell, the synthetic mRNA essentially tricks the body into building some of the virus' molecules itself. The proteins don't actually form a full virus, so it doesn't become infectious, but the body's immune system still recognizes the proteins and builds a response against them. 

Inovio, on the other hand, is testing a DNA-based vaccine—again, by injection—against the spike protein of the new coronavirus. Biotechnology company Novovax is doing something a little different: Its NVX-CoV2372 “subunit vaccine,” which showed promising results in animal trials, involves injecting only one part of the virus—the spike protein—into the body, to create antibodies that can protect against the coronavirus. 

Who can take part in a COVID-19 vaccine trial? 

Around the world, thousands of people are taking part in human trials to try to find a successful vaccine for the new coronavirus. According to Jansen, for stage one of the Phase 1/2 trial within Pfizer and BioNTech’s US clinical program, the aim is to enroll up to 360 healthy volunteers. “This may scale to more than 8,000 healthy participants by its conclusion,” she adds. The Inovio trial consists of 40 people in Phase 1 and “likely several thousand in Phase 2/3," Richardson says.  

Before taking part in a COVID-19 vaccine clinical trial, each participant has to go through a specific screening process. “Only people who have had no exposure to COVID-19 (established through antibody testing) will be allowed to participate,” Jansen says. “Volunteers will be pre-screened for the absence of antibodies against SARS-CoV-2 to show no history of past infection and no active infection within 24 hours of vaccination.”

Every trial has its own eligibility criteria, but across the board, younger, healthy adults are being immunized first. In the Pfizer/BioNTech's US research program—conducted by NYU Langone Health—older adults (age 65 to 85) will only be immunized with a vaccine candidate once testing in younger adults (age 18 to 55) has provided early evidence for safety and desired immune response.  

Being part of a COVID-19 vaccine clinical trial shouldn’t impact on someone’s life too much, but it’s important to continue to follow all public health guidance. Jansen warns that participants shouldn’t assume they’re protected and then engage in behavior that puts them at higher risk for infection. Researchers also check in with participants regularly, Richardson says. This is done both in person at the testing sites and electronically, over email and/or phone. 

Are there any downsides to participating in a COVID-19 vaccine trial?  

There hasn't been enough data gathered on any of the COVID-19 human vaccine trials to understand what the full spectrum of side effects are. However, it’s reasonable to expect some of the common vaccine side effects, like injection site soreness, achiness and fever, Dr. Adalja says. "It will take some time to understand the full side effect profile because not all of them are immediate and you have to follow study participants for a period of time to really get a full grasp," he adds. 

Jansen says the Pfizer/BioNTech participants will be followed-up throughout the entire study. "Safety is our number one priority," she says. "We work closely with trial volunteers and regulatory agencies worldwide to ensure we’re developing safe and effective vaccines. All participants are closely monitored for 24 to 26 months after the first dose of the vaccine."

“The phased clinical testing approach has been designed by the authorities to ensure that the safety of vaccines is of paramount importance,” Richardson says. “We test extensively in animals in advance of clinical testing too to look for safety signals.” 

Before you’re even screened for a vaccine clinical trial, the trial staff should explain the trial in detail and give you the opportunity to ask any questions you may have. If you agree to take part, you sign an informed consent form (ICF), which includes information of all potential risks of the trial. 

How is a COVID-19 vaccine trial different than a typical vaccine trial? 

The big difference between the current COVID-19 vaccine clinical trials and other vaccine trials is timescale. “Traditionally, we can spend years studying an emerging pathogen before defining a vaccine candidate and designing clinical trials to test it,” Jansen says. “However, with the SARS-CoV-2 pandemic already raging for months, a vaccine is needed urgently to protect communities from the virus that causes COVID-19." This is why Pfizer and BioNTech are testing not one but four different candidates. 

As a growing number of vaccine clinical trials get underway throughout the world, the big question everybody wants the answer to is, when will a vaccine be available? Researchers from the US and the UK have said that a vaccine might be available for emergency use as early as September. "Our Phase 1 trial will take one year, which is very typical of a clinical vaccine trial,” Richardson says. “However, we will use early data readouts to move very rapidly into efficacy testing.” 

That being said, it’s important to know that the entire vaccine development process—of which the clinical trials form only one part of many—often takes 10 to 15 years, per The College of Physicians of Philadelphia

That's why Dr. Adalja remains cautious. “While it is in the realm of possibility, it’s very daunting to think of a vaccine being available in September. For this to happen, everything would have to go perfectly. Vaccine development is something that is usually measured in years, not months. If a vaccine was available by September, it’s important to remember that the quantity wouldn’t be enough for the entire world—but possibly healthcare workers could be vaccinated.”

The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDCWHO, and their local public health department as resources.

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