As COVID-19 cases continue to spike across the United States and the rest of the world, several pharmaceutical companies have reached their final lap in the race to approve and distribute a COVID-19 vaccine — a vaccine from Pfizer and BioNTech received emergency authorization from the Food and Drug Administration on Dec. 11, and the FDA is expected to authorize Moderna’s vaccine by the end of the month.
However, amid rampant misinformation, politicization and general distrust of the vaccine development process, many Americans have expressed hesitancy over whether a COVID-19 vaccine would be safe and effective for widespread use.
To investigate these concerns, The Sun spoke with Cornell virologist Prof. Gary Whittaker and Prof. John Moore, microbiology and immunology at Weill Cornell, who explained the inner workings of COVID-19 vaccine mechanisms and their development.
How vaccines protect the body against COVID-19
According to Moore, vaccines are all designed to fulfill the same purpose of triggering the body’s immune system to produce antibodies against a specific target.
A critical component of immune defense, antibodies are proteins that recognize and neutralize foreign substances like bacteria and viruses.
“The antibodies that are raised recognize the virus and prevent it [from] infecting cells in the human body, therefore rendering the virus essentially harmless,” Moore said.
Moore explained that although current major candidates for the coronavirus vaccine have been designed in various ways, all of them have targeted a specific part of the virus — the spike protein.
This protein, a component of the outer surface of the virus membrane, enables the virus to latch onto target human cells expressing a specific receptor protein called ACE2. The coronavirus can bind to these receptors, providing an access point to penetrate human cells and replicate, resulting in infection, Moore said.
According to Moore, antibodies against the coronavirus can prevent infection by binding to the virus spike protein, which can interfere with the process of attaching onto the ACE2 receptor and halt viral entry into the cell.
“With that in mind, what the vaccine designers do is present a protein to the immune system in a way that does not cause virus infection,” Moore said. “The vaccines are harmless from that perspective. But the [spike] protein is presented to the immune system in a way that the immune system raises antibodies against it.”
Antibodies produced from vaccination can then remain in the body for extended periods of time, providing long-term protection from infection.
Vaccines essentially work like fire drills that can prepare the body in the event of a real “fire,” which would be the presence of the coronavirus inside the body, according to Whittaker.
“[We] train the body to get ready to fight off this disease … but it’s not actually the disease, it’s the safe version. So we get the response without the disease,” Whittaker said. “And so the immune system is trained and triggered. When the virus does come, there’s the immediate response.”
The vaccine development process, from start to finish
Although initially much was unknown about SARS-CoV-2, Moore said there was substantial pre-existing research on vaccine design, coronavirus biology and spike protein properties that could be quickly repurposed to develop a COVID-19 vaccine.
“The research community did not start from scratch,” Moore said. “It had blueprints that could be exploited and those blueprints were put in place by decades of research on immunology, protein production, vaccine design and development in general.”
After extensive research and design, vaccine developers have to make it through multiple, rigorous stages of testing and clinical trials before potential vaccines can be distributed to the population.
The first step, Moore said, is preclinical testing. This process can involve DNA sequencing and analysis based on basic laboratory techniques, as well as testing the vaccine against specific conditions set up in the lab.
Upon promising results from preclinical experiments, vaccine candidates can graduate to animal experiments, according to Moore. These experiments typically involve vaccinating small mammals, such as mice, rabbits, and guinea pigs — or if available, macaque monkeys — to model how humans might respond to the same vaccination.
“The goal in those initial studies was to assess whether they induce the right antibody responses, and whether there [were] immediately obvious safety considerations. That would be a major red flag,” Moore said.
Animal experiments can also be used to test different vaccine doses, as well as the spacing between doses to determine what could be the safest and most effective protocol for vaccination in humans.
The FDA must then approve the final vaccine product, and production will move out of the lab and into the hands of industry partners that have the capability to manufacture vaccines under conditions of very high quality and safety, Moore said.
To accelerate the typically years-long vaccine development process, Moore said vaccine manufacturers began large-scale production in tandem with the testing process.
“While some basic experiments were being done in animals, the best estimate of the optimal design was being produced under these large scale, ultra high quality conditions,” Moore said. “So then, you get into a position where you’re able to do a phase one clinical trial.”
Clinical trials and FDA approval
Phase 1 clinical trials are designed to test for the safety of the vaccine in humans, according to Moore. Approximately 50 people might be immunized during this stage, when researchers closely observe participants for any serious adverse reactions to the vaccine.
Researchers also test patients’ immune response by measuring the antibodies and immune cells that would have been triggered by the vaccine to gauge the vaccine’s initial performance, Moore said.
The FDA can then determine whether the study can move to Phase 2, which involves hundreds of patient volunteers, Moore said. This phase explores dosage regimens and timing, and further examines safety and the magnitude of patients’ antibody responses.
If Phase 2 is successful, Moore said the study can receive approval to start Phase 3, during which tens of thousands of patients are immunized and a control group receives a placebo, and the rate of infection is compared between the two groups. This larger scale experiment can test the vaccine for efficacy.
According to Moore, the efficacy of a vaccine is determined by how many of the infected patients received the placebo compared to those who received the vaccine. For example, if a Phase 3 study resulted in 100 infections, 95 percent efficacy would mean that 95 of those infections were participants in the placebo group, while the remaining 5 had received a vaccine.
Moore explained that current vaccine candidates have had promising results from Phase 3 clinical trials — especially in preventing severe disease and death.
“These severe disease cases have almost all been in the placebo group, including at least one death in the placebo group,” Moore said. “There’s fewer numbers here, but the data is suggesting that the vaccines are also protecting against severe disease and death, which would obviously be a good thing.”
Promising results from Phase 3 trials can allow vaccine manufacturers to apply for FDA approval, the current stage of several vaccine candidates.
In evaluating vaccine candidates for approval, Moore emphasized that the FDA will maintain high standards of integrity, despite the pressures the pandemic and political figures have placed on the process.
“These are leading scientists that are well respected in the field that people have experience and integrity. They will do a thorough evaluation procedure on the information that they’ve been given,” Moore said. “And they’ll make a recommendation to the FDA which could be rejected or it could be approved. And the likelihood is, that they’ll get approved.”
How the pandemic has accelerated vaccine development
In order to control the pandemic and return people’s lives back to normal as quickly as possible, Moore said that COVID-19 vaccine development has been greatly accelerated for a process that usually takes years, or even decades.
“It’s important to move as quickly as possible. But you also can’t compromise safety,” Moore said. “Because firstly, the public has to be confident that the vaccine has been approved through an appropriate process. And it needs to be transparent. And it needs to be free of political interference, which has been an issue all year.”
Whittaker agreed with Moore, noting that releasing a vaccine too soon could worsen issues of vaccine hesitancy and denial for an already skeptical population.
“We’ve got to be clear, we can’t be fast tracking too much and not being transparent and not doing the correct documentation,” Whittaker said. “Because we don’t want to release either a poor vaccine or worse, a bad vaccine….that will be very detrimental.”
However, Moore is confident that despite the acceleration of the vaccine development process, no corners have been cut when testing for safety or efficacy.
The major change that sped up COVID-19 vaccine development was the manufacturing of vaccines even prior to final approval of a candidate, according to Moore. This meant that federal governments in many countries pre-funded vaccine production, putting hundreds of millions — even billions — of dollars on the line on the off chance that a specific candidate is approved for safety and efficacy later on.
Normally, no pharmaceutical company would ever take such an enormous financial risk.
“Well, the government … took the financial responsibility off the companies and said, ‘Look, we’ll pay for this to be made, we’ll keep our fingers crossed, we’ll hope everything goes okay in the evaluation process. And if it does, we can roll the vaccines out now, instead of waiting six months to make them,’” Moore said. “So that’s a legitimate way to save a substantial period of time.”
An overview of current vaccine candidates, and how they work
There are currently three main subcategories of vaccines among leading vaccine manufacturers
The first and most prominent type of COVID-19 vaccine is the mRNA vaccine, which is utilized by pharmaceutical frontrunners Moderna and the Pfizer-BioNTech partnership.
Moore explained that mRNA is a set of instructions that the body can read to produce proteins. If a vaccine includes such instructions on how to make antibodies against the coronavirus, this can transform human cells into factories for making these antibodies, resulting in immunity against COVID-19 infection.
“mRNA vaccines are brand new. They’ve never been used before, but they’re seemingly very powerful and very, very efficient,” Whittaker said. “In a way, it’s really revolutionized vaccine technology in the process of dealing with the emergency of the pandemic.”
However, one major limitation of mRNA vaccines is their instability. Moore said that since mRNA is so fragile, it must be kept at extremely low temperatures and would require ultracold freezers, creating concerns over how vaccines can be distributed.
Moore said that although this creates a “logistical headache,” the problem is “not one that isn’t solvable.”
Britain recently approved the Pfizer-BioNTech mRNA vaccine for emergency use, and began vaccinating small numbers of healthcare workers and people over 80.
The FDA followed suit, granting emergency authorization to the Pfizer-BioNTech mRNA vaccine on Dec.11. The first shots of the COVID-19 vaccine were administered on Monday to New York healthcare workers, kicking off a massive vaccine rollout campaign against a pandemic that has claimed over 300,000 lives in the United States.
On Dec. 9, Canada approved the Pfizer-BioNTech vaccine for emergency use as well, starting its own inoculation program on Monday, with initial doses going to nursing home residents and health care workers.
A second type of vaccine is viral vector vaccines, in which viruses that cause the common cold — adenoviruses — are weakened to prevent infection, according to Whittaker. Genes encoding the coronavirus spike protein are then stitched into the genome of the adenovirus, Moore said.
Therefore, when the weakened adenovirus from the viral vector vaccine infects human cells, these cells begin to produce the coronavirus spike protein — which is recognized by the human immune system and triggers antibody production, Moore explained.
Viral vector vaccines have been approved for use in China and Russia, and another is currently in a Phase 3 clinical trial for the British-Swedish company AstraZeneca.
A third type of vaccine is the protein-based vaccine, in which the coronavirus spike protein is produced on a large scale, purified and injected directly into patients, Moore said. Novavax is the leading protein-based vaccine candidate in the U.S. and is currently in a Phase 3 clinical trial.
Although all three types of vaccines, among other types, accomplish the same task in different ways, scientists must wait for the results of Phase 3 trials for viral vector and protein-based vaccines before deciding whether one type is more effective than another, Moore noted.
Should people take the vaccine?
As vaccine distribution ramps up across the United States, the question remains: Should Americans be willing to take it? For Moore, the answer is a resounding “yes.”
“It’s important that these vaccines be used. And it’s important that the public trust them,” Moore said. “For the public to trust them, it’s important that the approval process must be seen to be both rigorous and transparent.”
Both Moore and Whittaker agreed that the public must have trust in science and public health officials, which will allow the vaccine to successfully protect people from COVID-19.
“If the FDA does its usual thorough job, then people need to get behind these vaccines and actually use them,” Moore said. “Because a vaccine that isn’t trusted is a vaccine that isn’t used, and a vaccine that isn’t used … is useless.”
Moore further implored people to have confidence in the FDA and tune out misinformation that has created distrust in the vaccine development process.
“The stuff on the internet that you can find in a quick Google search — most of it is rubbish,” Moore said. “So we have to rely on science, rely on media, or information sources that are reliable, and make appropriate judgments and not believe all of the junk that goes around.”