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September 21, 2020

How Close Are We to a Safe COVID-19 Vaccine?

How Close Are We to a Safe COVID-19 Vaccine?

Updated on September 21, 2020 at 11:15am EDT.

As the COVID-19 pandemic wears on, many people are pinning their hopes on a vaccine. Amid reports of reinfections and waning antibody levels among those who’ve recovered, many experts suggest that a vaccine may be the only way to safely re-open societies and achieve herd immunity—the threshold at which enough people have become immune to a germ so that it can no longer spread in communities.

On May 15, 2020, Operation Warp Speed was launched. This public-private partnership, which includes the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH), among other federal agencies and private firms, set a goal to produce and deliver 300 million doses of safe and effective vaccines starting in January 2021.

Several months ago, this lofty mission may have sounded like science fiction. Normally, vaccines take up to 20 years to develop. Since the beginning of the pandemic, scientists have been using cutting edge technology to slash that time to an estimated 1 to 1.5 years. 

More than 200 potential vaccines are in various stages of development around the world. So far, nine have begun or will soon launch phase 3 clinical trials. This is the last stage before a new medical treatment in the United States can seek FDA approval so that it may be made available to the public.

Vaccines for COVID-19 all work on the same basic principle: stimulate an immune response without causing real disease. But some of the top candidates are designed to do this in different ways.

So, how do they work, and which ones are farthest along in development?

mRNA vaccines. These vaccines deliver snippets of genetic material that carry instructions for making the COVID-19 spike protein—the protein that the coronavirus (SARS-CoV-2) uses to infect cells. The mRNA is packaged inside a slippery coating that allows it to slide into cells and tell them to make the spike protein. This prompts an immune response to protect you from catching COVID-19.

The mRNA vaccines are the newest kids on the block. In animal tests, they have shown promise for treating certain types of cancer and infectious diseases, such as the flu and Zika virus. So far, no mRNA vaccines are widely available for preventing infections in people.

Two mRNA vaccines for COVID-19 are now in phase 3 trials. The first was developed by Moderna in partnership with the NIH, and the second has been developed by Pfizer in partnership with Germany’s BioNTech and China’s Fosun Pharma.

Some 30,000 participants have enrolled in Moderna’s phase 3 trial. The company’s CEO reportedly announced on September 17, 2020 that it will become clear by November if its vaccine will be ready by the end of the year.

Pfizer’s phase 3 trial aims to expand its enrollment to up to 44,000 participants in order to include more minorities and those with stable HIV or Hepatitis C or B infections as well as teens as young as 16 years old. In a September 12, 2020 statement, the company stated it expects to know if its vaccine is effective by the end of October 2020.

Replication defective vaccines. For this type of vaccine, scientists delete genes that a virus uses to reproduce and cause illness. Some of these candidates being developed for COVID-19 use adenoviruses, which are a family of viruses that can cause cold-like symptoms.  

Scientists swap the replication genes in these viruses for genes that carry the message for making a COVID-19 protein that triggers antibodies and leads to immunity. In other words, the vaccine uses another type of harmless virus to deliver biological instructions for how to fight off the coronavirus that causes COVID-19.

One drawback, however, is that experience is limited with this type of vaccine. No replication defective vaccines are widely available for people, although promising ones have been developed to protect against Ebola virus.

Three replication defective COVID-19 vaccines have started or will soon launch phase 3 trials.

One known as AZD1222 emerged early on as a leading contender in the global vaccine race. This vaccine is being developed by AstraZeneca in partnership with the University of Oxford.

AstraZeneca launched the final stage of its trial on September 1 with plans to test the vaccine in 30,000 healthy adults with diverse racial and ethnic backgrounds. The trial was abruptly halted on September 8, however, due to a possible adverse reaction in the U.K. The reaction was reportedly consistent with a condition called transverse myelitis, or spinal cord inflammation. The event is currently under review, pending an official diagnosis. Meanwhile, the trial has resumed in the U.K., Brazil and South Africa but remains paused in the United States.

Keep in mind, this is standard protocol, or what happens whenever a negative event is documented in a clinical trial. It’s also still unclear if this reaction is associated with the experimental vaccine, or if it’s an unrelated issue.

The second vaccine of this type was developed in China and received early approval for military use in China in June. The third was developed in Russia and has received provisional early approval. Phase 3 trials for the Chinese and Russian vaccines are expected to start at the end of September 2020.

Inactivated or attenuated coronavirus vaccines. Attenuated vaccines use weakened forms of a virus, while inactivated vaccines use killed forms of the virus. Both types are developed so that they cannot actually cause disease but still trigger an immune response to generate immunity.

Three of these types of vaccines are in phase 3 trials. All three have been developed by Chinese researchers. Two of these vaccines have been granted emergency approval for use by healthcare workers in the United Arab Emirates.

Repurposed vaccines. Scientists are also evaluating vaccines that are already used for other infectious diseases. So far, the only one of these in phase 3 trials is the bacillus Calmette-Guerin vaccine, which was developed in the early 1900s for tuberculosis. This vaccine is being tested in Australia.

Why speed isn’t compromising safety
The million-dollar question is whether fast-track development of a COVID-19 vaccine could compromise safety and efficacy.

Procedures are in place to catch problems, if they crop up, according to Paul Offit, MD, director of the vaccine education center and a professor of vaccinology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. Dr. Offit is also the co-inventor of RotaTeq, a vaccine credited with profoundly decreasing global childhood death from the rotavirus microbe that causes severe diarrhea and dehydration.

The biggest safeguard is the phase 3 trials themselves, Offit says. Each trial has a data and safety monitoring board that checks for adverse events possibly related to the medical treatment under investigation.

If the boards identified one, they stop the trial, which is what happened with AstraZeneca’s replication defective COVID-19 vaccine.  

Phase 3 trials usually include tens of thousands of people, making them large enough to pick up some rare side effects of a new drug, but not necessarily all of them. More rare side effects often don’t appear until millions of people have taken a new drug. That’s why drug makers are required to continue monitoring a new treatment even after the FDA approves it, Offit explains.

The other major safeguard is the FDA’s vaccines advisory committee, which reviews each trial’s data to make sure that it’s safe and effective. 

“Then and only then would we recommend it for use by the public,” Offit says.

Yet in the midst of an election year, concerns have been raised that politics may sway decisions about vaccine approvals.

“It’s an understandable concern,” Offit notes. “One can’t help but feel that the FDA was pressured to approve hydroxychloroquine and convalescent plasma.”

But he added that both the FDA vaccines advisory committee and each trials’ data and safety monitoring board are set up to be divorced from politics.

“Members of those groups are not government associated nor are they pharmaceutical company associated,” he explains. “That’s an independent review. I think one can trust that independent review.”

Ultimately, Offit says that it’s too early to say anything about the efficacy and safety of these vaccine candidates. To really know the answers, we’ll need to wait for results from the phase 3 trials.

“We should know about those in the next couple of months,” he says. “To make sure that these vaccines are being held to a high standard of safety and efficacy, wait for the data.”

Medically reviewed in September 2020.

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