Finally, we have an approved vaccine for COVID-19. Experts say widespread vaccination could help bring the deadly pandemic to its knees, so this seems like the light at the end of the proverbial tunnel. But there are still a lot of unknowns.
A year ago, the world hadn't even heard of COVID-19, much less SARS-CoV-2 (the novel coronavirus that causes the illness). When you consider that vaccine development typically stretches over years, not months, it's remarkable we're even talking about lining up for shots.
But developing, manufacturing and deploying hundreds of millions of doses of vaccine is a mammoth undertaking, and there are bound to be slowdowns and other glitches along the way. Here, experts describe some of the challenges a COVID-19 vaccine must overcome.
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History Shows There's No Guarantee of Success
While the FDA has given Pfizer and Moderna the green light on their vaccines, others are still in progress. And the more effective vaccines we have at our disposal, the better, because there are so many people to vaccinate (including children under 16 — the vaccines approved so far won't be available to them).
But vaccine development is a painstaking process, and it doesn't always pay off. A March 2013 PLOS One study looked at risks involved in vaccine research and development and found that the average vaccine takes nearly 11 years to develop and has a 6 percent chance of entering the market.
Sometimes even the most concerted efforts fall flat. An August 2013 Vaccine review traces global initiatives to develop a vaccine against human immunodeficiency virus, the virus that causes HIV/AIDS. After more than three decades, we still don't have a vaccine to prevent these infections.
Hoping to shorten the time it takes to develop and deploy vaccines, the federal government in May launched Operation Warp Speed, an unprecedented initiative allowing vaccine developers to perform certain tasks simultaneously, rather than sequentially. The aim is to accelerate vaccine development "without curtailing the critical steps required by sound science and regulatory standards," according to an October 2020 editorial in The New England Journal of Medicine.
Still, these things take time to get right, and the path to an effective vaccine is typically filled with twists and turns.
It Has to Be Protective
No vaccine is 100 percent effective, according to the World Health Organization. Annual flu vaccines, for example, reduce the risk of influenza by 40 to 60 percent, per the Centers for Disease Control and Prevention (CDC).
So, what level of protection should a COVID-19 vaccine provide? The U.S. Food and Drug Administration (FDA) is looking for vaccines that can prevent disease or decrease its severity in at least 50 percent of people who are vaccinated.
"That's the minimum threshold for emergency use authorization," says Amesh Adalja, MD, senior scholar at the John Hopkins Center for Health Security in Baltimore.
But is that good enough?
Using computer modeling to simulate the spread of COVID-19, researchers recently looked at the effect a vaccine could have under various conditions. Assuming 75 percent of the population gets vaccinated, a vaccine must have an efficacy of at least 80 percent to snuff out an ongoing epidemic, they reported in the July 2020 issue of the American Journal of Preventive Medicine. That's what would be needed to return to normal — meaning no more masks, no more social distancing.
That doesn't mean a vaccine with lower efficacy isn't useful, the study authors say. Even if it fails to wipe out the epidemic, "it can still save a considerable number of lives, hospitalizations and costs," they explain. Plus, vaccination could be combined with other mitigation measures, like mask-wearing, the authors point out.
Proof of Safety Is a Must
Vaccine development in the U.S. involves multiple levels of safety checks, beginning with testing in cells or tissues and animals, according to the College of Physicians of Philadelphia. Only promising vaccine candidates move on to human trials.
Phase 1 trials look at safety and the immune response a vaccine candidate provokes in a small group of people. Phase 2 trials involve several hundred people. In phase 3, tens of thousands of people are randomly assigned to receive the experimental vaccine or a placebo.
Success in early human trials doesn't mean a vaccine is destined for approval. Phase 3 trials can reveal certain rare side effects that might not surface in smaller phase 1 and phase 2 studies, per the College of Physicians of Philadelphia.
To assess the risk versus benefit of a COVID-19 vaccine, the FDA intends to review at least two months of phase 3 data after trial participants have completed their final dose.
"Usually most side effects of vaccines happen in the first four to six weeks," says Hana El Sahly, MD, associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, a phase 3 testing site for Moderna's vaccine.
Once safety data is reviewed and the FDA gives the nod, "we're pretty sure that there aren't going to be adverse events popping up left and right," says Arthur L. Caplan, PhD, professor of bioethics at the New York University Grossman School of Medicine in New York City.
Also, it's in companies' best interest to assure their vaccines are safe. "If they put out a vaccine and it gets into safety trouble, they're going to lose a lot of money and they're going to lose a lot of investors," he tells LIVESTRONG.com.
Compliance May Be a Problem
Both the Pfizer and Moderna vaccines require two doses, and so do several other COVID-19 vaccine candidates. After the first shot, a second is given a few weeks later.
The problem is that some people may not bother getting a second shot or presume they're done after the first dose. In the history of vaccines, "anything that's been a two-shot vaccine has turned out to be a pain in the neck. People don't comply," Caplan pointed out during a media briefing on the topic.
Some people might sit out vaccination altogether. Only about half of U.S. adults are willing to take a COVID-19 vaccine once it's available, according to Pew and Gallup polls. That's down 21 and 16 points, respectively, from surveys the two research outfits conducted in the spring and summer. The polls suggest public support for a COVID-19 vaccine may not reach 70 percent, the minimum level experts say may be needed to achieve "herd immunity."
To overcome vaccine hesitancy, public health officials might want to consider outreach strategies to address the concerns of people who are more susceptible to the infection, researchers concluded in an October 2020 study in JAMA Open Network.
Alternate Dosing Strategies May Get More People Vaccinated, but There's No Guarantee of Effectiveness
Officials are working to deliver the vaccine to the public as quickly as possible, and there have been discussions about changing the FDA-approved vaccine dosing and schedules in an effort to immunize more people in less time.
One such suggestion involves reducing the number of doses to a single shot. But we don't have enough information to suggest that people will be protected for the long term following a single dose, John P. Moore, PhD, professor of microbiology and immunology at Weill Cornell Medical College, tells LIVESTRONG.com.
Without the clinical data, "we cannot conclude anything definitive about the depth or duration of protection after a single dose of vaccine," according to the FDA.
Another possible strategy for getting the vaccine to a greater number of people is delaying the second dose. This altered dosing schedule is being adopted by Britain, where the second dose can now be given up to 12 weeks after the first. The idea is to offer at least partial protection to a larger portion of the public.
Unfortunately, this plan, like the single-dose approach, doesn't have enough science to support it, Moore says. The main issue is that antibodies to the COVID-19 vaccines lessen over time, which means that antibody levels may not be protective for up to 12 weeks.
What's more, this tactic may cause wider consequences for public health.
"If people do not truly know how protective a vaccine is, there is the potential for harm because they may assume that they are fully protected when they are not, and accordingly, alter their behavior to take unnecessary risks," per the FDA.
To make matters worse, weak antibody responses in a large pool of insufficiently vaccinated people could contribute to the emergence of virus variants that may be vaccine-resistant, Moore says. With at least two new strains — which might be more transmissible — already circulating globally, this is not a problem we want to create.
The third option is to halve the dose of each shot, which would theoretically double the supply of vaccine. While, again, there's no scientific evidence to support this dosage change as of yet, some of the clinical trial data suggests administering two half-doses could provide sufficiently strong antibody levels, Moore says.
But there are more grounds to believe that this half-dose would work for the Moderna vaccine (which uses a 100-microgram dose) versus the Pfizer (which uses a 30-microgram dose), says Moore, explaining that reducing the larger dose permits more margin for error. Still, more research is needed to validate this hypothesis, which is why the FDA doesn't currently back this altered regimen of dosing either.
Lastly, some officials have proposed mixing and matching vaccines in certain cases. For instance, in Britain, if a second dose of the vaccine a person originally received isn't available, another vaccine may replace it.
The major problem with this mix-and-match regimen is there's zero information about it. "Literally no data anywhere, including in animal model literature," Moore says.
In fact, the CDC explicitly states "these mRNA COVID-19 vaccines are not interchangeable with each other" and "both doses of the series should be completed with the same product."
Here's the takeaway: To ensure the safety and efficacy of the vaccine, it must be administered exactly as it was studied in the clinical trials until additional studies are available to suggest otherwise. "Guessing your way to solutions is not the right way to do science," Moore says.
People May Need a Booster Shot
How long will a COVID-19 vaccine last? It's a question vaccine researchers — people like Kirsten Lyke, MD, professor of medicine at the University of Maryland School of Medicine in Baltimore — are trying to answer.
She's been on the front lines of clinical trials of two different vaccines. Each uses messenger RNA, an approach she likens to delivering a bit of computer code into a cell, instructing it to make spike protein (the type found on the surface of SARS-CoV-2). When the body's immune system encounters the protein, it makes antibodies. It's teaching your immune system to recognize COVID, she says, so that when you encounter the virus, your immune system ramps up quickly.
"We know that it can make good protein and we know it can make good neutralizing antibodies, which are really key for respiratory viruses, but we don't know how long that'll last," Dr. Lyke says.
What if a vaccine imparts immunity, but it only lasts six months? People would need booster shots, creating additional expense and distribution hassles, Caplan points out. We might even learn that the vaccine lasts for a shorter period of time in certain populations. It may fade faster in older adults, for example. "You might have to re-vaccinate them every three months," he says.
It's a Huge Logistics Challenge
In a typical year, the CDC distributes vaccines for more than 80 million people, according to director Robert Redfield, MD, who testified before a Senate subcommittee this summer. In an emergency, the CDC can scale up to distribute up to 900 million vaccine doses, he noted. So, for a two-dose vaccine, do the math: It will take 660 million doses to vaccinate all 330 million Americans.
Under Operation Warp Speed, the goal was to stockpile hundreds of millions of doses by the end of 2020, according to the New York Times. In reality, the number of doses that will be ready to go may be far fewer.
Making enough vaccine is one challenge; getting it out to the masses is another.
"Distributing potentially hundreds of millions of doses of COVID-19 vaccines rapidly, effectively and equitably represents a public logistics effort on a scale not seen in the U.S. before," according to a Kaiser Family Foundation analysis.
Vaccines must be kept under tightly controlled temperatures from the time they're made to when they're administered, explains Anna Nagurney, PhD, professor in the Department of Operations and Information Management at the University of Massachusetts Amherst. Some COVID-19 vaccines require freezing temperatures — a frigid minus 94 degrees, in the case of Pfizer's vaccine. Maintaining the "vaccine cold chain" will require careful coordination and investment.
"Not every health care facility is equipped with very low-temp refrigerators," she tells LIVESTRONG.com.
There's Big Money Involved
Congress has already committed $10 billion in taxpayer money to COVID-19 vaccine development and manufacturing, according to the U.S. Department of Health and Human Services. A Bloomberg report suggests, however, that Operation Warp Speed's budget may have swelled to as much as $18 billion.
Pfizer did not receive government money to develop or manufacture its two-dose vaccine. But under a $1.95 billion agreement with the U.S. Department of Health and Human Services and Department of Defense, it will deliver 100 million doses to the government. And the government has an option to purchase an additional 500 million doses.
Vaccine doses purchased with taxpayer dollars will be given to Americans at no cost, according to the CDC. If there's a fee for administering the shot, it'll be reimbursed by insurance, it says. Public health clinics may offer free vaccines for people who are uninsured.
So, while most people, at least initially, won't have to pay out-of-pocket for their first doses, with the Pfizer vaccine, "you might," Caplan says.
When Can People Get Vaccinated?
It may be a while before the first doses are widely available. HHS Secretary Alex Azar recently predicted that there would be enough vaccine for all Americans who want one by spring 2021, per CNN.
If that timeline holds up, it would be an amazing accomplishment. By this time next year, perhaps multiple vaccines will be available, experts say.
In the meantime, we all need to do our part to slow the spread of the infection, and that means continued mask-wearing, hand-washing and social distancing.
— Additional reporting by Jaime Osnato
Read more stories to help you navigate the novel coronavirus pandemic:
Is This an Emergency?
- JAMA Network: "Coronavirus Update With Anthony Fauci — October 28, 2020"
- PLOS One: "Risk in Vaccine Research and Development Quantified"
- Vaccine: "A Brief History of the Global Effort to Develop a Preventive HIV Vaccine"
- The New England Journal of Medicine: "Developing Safe and Effective Covid Vaccines — Operation Warp Speed’s Strategy and Approach"
- World Health Organization: "Six Common Misconceptions About Immunization"
- Centers for Disease Control and Prevention: "How Well Do Flu Vaccines Work?"
- U.S. Food and Drug Administration: "Emergency Use Authorization for Vaccines to Prevent COVID-19"
- American Journal of Preventive Medicine: "Vaccine Efficacy Needed for a COVID-19 Coronavirus Vaccine to Prevent or Stop an Epidemic as the Sole Intervention"
- Pew Research Center: "U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine"
- Gallup: "Americans' Readiness to Get COVID-19 Vaccine Falls to 50%"
- JAMA Open Network: "Factors Associated With US Adults’ Likelihood of Accepting COVID-19 Vaccination"
- College of Physicians of Philadelphia: "Vaccine Development, Testing, and Regulation"
- Senate Committee on Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies: "Review of Operation Warp Speed: Researching, Manufacturing, & Distributing a Safe and Effective Coronavirus Vaccine"
- New York Times: "For Trump, G.O.P. Created an Alternative America Beyond Covid-19"
- Johns Hopkins University + University of Washington: "Preserving the Scientific Integrity of Getting to COVID-19 Vaccines: From Clinical Trials to Public Allocation"
- Kaiser Family Foundation: "Distributing a COVID-19 Vaccine Across the U.S. - A Look at Key Issues"
- CNN: "Dr. Anthony Fauci Reacts to Pfizer's Vaccine Announcement"
- Pfizer: "Pfizer and BioNTech Announce Vaccine Candidate Against COVID-19 Achieved Success in First Interim Analysis From Phase 3 Study"
- Moderna: "Moderna Has Completed Case Accrual for First Planned Interim Analysis of its mRNA Vaccine Against COVID-19 (mRNA-1273)"
- U.S. Department of Health and Human Services: "Fact Sheet: Explaining Operation Warp Speed"
- Bloomberg: "Trump Administration Dips Into Protective Gear, CDC Funds to Fund Vaccine Push"
- Pfizer: "Pfizer and BioNTech Announce an Agreement with U.S. Government for Up to 600 Million Doses of mRNA-based Vaccine Candidate Against SARS-CoV-2"
- CDC: "Frequently Asked Questions about COVID-19 Vaccination"
- CNN: "Vaccine Could Be Available to "All Americans" by Early April, Azar Says"
- The New York Times: "Why the U.K. Approved a Coronavirus Vaccine First"
- U.S. Food and Drug Administration: “FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines.”
- Centers for Disease Control and Prevention: “Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States.”