The COVID-19 vaccines coming soon to the United States and already approved in the U.K. and Canada are the fastest vaccines ever created.
In a remarkable achievement of medical science, we’ve gone from identifying a new pathogen — the novel coronavirus known as SARS-CoV-2 — to discovering an immune response against it to developing and testing a safe and effective vaccine for it in less than 12 months.
Previously, the fastest vaccine to go from development to deployment was the mumps vaccine in the 1960s, which took about four years.
“This is shattering that record,” says Otto Yang, MD, an infectious disease specialist at UCLA Health.“This is really an amazing achievement.”
It’s also one that may have implications for future vaccine development, he says, because of the new technologies involved.
So how were scientists able to create a safe and effective vaccine in record time?
Some of the groundwork actually started decades ago, long before the first cases of a mysterious pneumonia surfaced in China in December 2019.
“The reason we are here, less than a year into the pandemic and we have two effective vaccines, is because of what came before this — efforts to develop vaccines for HIV or MERS or SARS or Ebola,” says Eric Daar, MD, chief of HIV Medicine at Harbor-UCLA Medical Center. “People developed these novel strategies while pursuing vaccines for these other diseases, so they were basically on the lab bench waiting for the next pandemic to come along.”
The COVID-19 vaccines from Pfizer, Moderna and AstraZeneca make use of two of these new strategies, or “platforms,” which makes them unlike any other commonly used vaccines. Most familiar vaccines — against flu, measles or tetanus, for example — rely on inactivated viruses (flu and tetanus) or weakened virus strains (measles, mumps), says Dr. Yang. Some vaccines, such as the one for hepatitis B, employ artificial proteins created in a lab. Each of these strategies requires development specific to the exact virus or bacterium.
But the leading COVID-19 vaccine candidates use none of these traditional methods to deliver genetic information to cells. Instead, they’re based on what Dr. Yang describes as a “plug-and-play” approach.
As soon as the novel coronavirus was identified and sequenced in China, its genetic information was plugged into existing vaccine platforms scientists were developing for other diseases.
“The platforms were already there and all the conditions were set,” Dr. Yang says. “So it’s just a matter of taking the sequence you want to insert and inserting it.”
Messenger RNA, viral vectors and spike protein
Messenger RNA and viral vectors are the new platforms at work in the COVID-19 vaccines likely to be authorized for emergency use by the U.S. Food and Drug Administration in the coming weeks.
The Pfizer and Moderna vaccines are based on the messenger RNA, or mRNA, platform. Hungarian biochemist Katalin Karikó — now a senior executive with BioNTech, Pfizer’s partner on the COVID-19 vaccine — started developing mRNA therapies in 1990 while a professor at University of Pennsylvania Medical School.
RNA is temporary genetic information that instructs a cell to make a protein, Dr. Yang says. “Normally, a cell uses its own RNA to make cell proteins for its own functions,” he says. “When a cell is infected by a virus, the virus will insert its genetic material, either RNA or DNA, and the cell becomes a virus factory because that genetic material is used to tell the cell to make viral proteins.”
In the COVID-19 vaccines, the mRNA platform delivers genetic information that tells cells to make spike protein, named for the spikes on the surface of the coronavirus. Production of this protein stimulates the immune system to produce antibodies to combat coronavirus, just as it would in the case of actual infection.
“All vaccines work by mimicking the infection and having the immune system do what it does naturally,” Dr. Yang says. “So if you get SARS-CoV-2, your immune system makes antibodies to fight the infection. What you’re doing with the vaccine is basically putting the immune system through its normal paces in terms of how it reacts — you’re giving the immune system a version of what it would encounter if you were infected but without the disease.”
To protect against COVID-19, vaccine recipients are being given genetic information to make spike protein, which is enough to stimulate an immune response. There’s no coronavirus in the coronavirus vaccines.
The AstraZeneca vaccine achieves the same aim using a different platform. Called a viral vector, it relies on a weakened adenovirus, a generally mild virus that causes the common cold to deliver genetic information to cells. The body sees the adenovirus and follows the inserted genetic instructions to produce spike protein, thus triggering an immune response.
Determining safety and efficacy
Vaccines need to be safe and effective to be useful, and the extreme transmissibility of COVID-19 actually expedited vaccine research.
“In order for something to really get studied, it has to be very prevalent,” says Annabelle De St. Maurice, MD, MPH, co-chief infection officer for UCLA Health. Dr. De St. Maurice recalled that efforts to create a vaccine for Zika virus stalled when disease numbers naturally diminished — there weren’t enough infections to sustain large-scale trials.
That hasn’t been the case with COVID-19.
“Unfortunately, we’ve not had any lag in viral transmission,” she says. “The upside to that, though, is that it provides opportunity to study vaccine efficacy.”
To test whether a vaccine works, scientists look at volunteers who’ve received the vaccine and volunteers who received a placebo to see how many in each group get sick. With COVID-19 spreading so quickly, reaching sufficient disease numbers to measure efficacy happened in just a few months.
Very few of the volunteers in either the Pfizer or Moderna vaccine groups developed COVID-19 symptoms compared to placebo groups.
With tens of thousands of volunteers involved in these two trials and no serious adverse events, the resulting safety data is reliable, too, Dr. De St. Maurice says.
“The goal of the FDA is to make sure that this is a safe vaccine. The last thing anyone wants is to rush something out that is unsafe,” she says. “If the FDA says it’s safe and they recommend it for health care workers, I will take the vaccine.”
Some side effects have been reported with the new vaccines, including fever, fatigue, headache and muscle aches. Britain’s medical regulator said on Dec. 9 that people with a history of severe allergic reactions should not take the Pfizer vaccine after two recipients there had such responses. They have since recovered.
“It’s all worth it in the end if it protects you from getting sick,” Dr. De St. Maurice says. “I’d rather have that for a day than for weeks or months from COVID.”
That these new vaccines appear to deliver effective protection against the coronavirus without severe side effects is promising for the broader field of infectious diseases, Dr. Yang says.
“Hopefully, looking at the big picture, this is more than an achievement just for COVID-19,” he says. "These are platforms that are readily deployed — for the next pandemic or even for existing viruses. Maybe these could actually improve vaccines overall.”
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