It’s the end of summer. COVID-19 has been with us for at least seven months in the United States. People are tired. School reopening is messy. And everyone is still hoping for a vaccine—including me. I’d like nothing more than for life to return to some semblance of normal, and to feel that my family is protected from this virus without having to avoid friends and other loved ones. But I’m also cautious. While I’d love a vaccine tomorrow, I understand that the development of a safe and effective vaccine takes time.
When I first wrote about the vaccine back in March, the vaccine development process was just beginning. Now, at press time, we are nearing 200 vaccines somewhere in the development pipeline, according to the New York Times’s vaccine tracker. The vast majority of those—about 135 candidates—are in pre-clinical development, meaning they are still being tested in cells or animals before human trials begin. Twenty-one are currently in Phase 1 testing, meaning they’re being tested on a small number of people to look at safety and to determine the optimal dose. Thirteen are in Phase 2, which tests the potential vaccine in a larger group of individuals to further look at safety. Both Phase 1 and 2 can also examine the immune response of vaccine recipients to see if they are generating antibodies and otherwise responding as expected.
Phase 3, then, are larger studies with tens of thousands of volunteers. These also look at safety, but this is really where we start to find out if the vaccine works and protects people from infection. There are eight candidates in some part of this phase. Finally, there are actually two vaccines already approved for limited use—one from the Chinese company CanSino biologics, which the Chinese military approved in June, and one from the Russian Gamaleya Research Institute, which Russian President Vladimir Putin said was approved in August. After backlash about a lack of safety and effectiveness evidence, the Russian government said the vaccine was approved with a “conditional registration certificate” contingent on Phase 3 trials. (Putin, however, did say one of his daughters had received the vaccine, according to the New York Times.)
So what does all of this mean in terms of having a safe, effective vaccine as soon as humanly possible?
To figure out what experts think of the vaccines currently under development and when we might have access to them, I chatted with Angela Rasmussen, Ph.D., a virologist at Columbia University who has published research on coronaviruses; Alyson Kelvin, Ph.D., a virologist at Dalhousie University who focuses on respiratory viruses; and Juliet Morrison, Ph.D., a virologist at University of California, Riverside, who studies host-virus interactions. Here are their answers to the most common COVID-19 vaccine questions.
First: Which vaccines look the most promising?
It’s tough to come to a consensus at this point, with so much still up in the air and no completed Phase 3 trials yet. Rasmussen notes that we should have data on one or more of these Phase 3 vaccines by late 2020 or early 2021. Kelvin explains that six of these vaccines have thus far received financial and logistical support from the American government through Operation Warp Speed, the nickname for the government’s goal of delivering 300 million doses of a safe and effective COVID-19 vaccine to the U.S. public by January 2021.
Various potential COVID-19 vaccines rely on different types of technology using different antigens, or portions of the SARS-CoV-2 virus that can stimulate an immune response. Some candidate vaccines use viral vectors, where genes from SARS-CoV-2 are inserted into harmless viruses for the immune system to recognize. This includes the AstraZeneca/University of Oxford vaccine and the Johnson & Johnson vaccine. Two other candidate vaccines (from Moderna and Pfizer) use mRNA technology, which involves injecting the protein-encoding part of SARS-CoV-2 into the body so that our own cells produce the foreign protein and develop an immune response against it. Two other candidate vaccines from Noravax and Sanofi-GSK use proteins from SARS-CoV-2.
The mix of different types of vaccine candidates and manufacturers will theoretically make it more likely that at least one will have a successful Phase 3 trial. Even those that may look good in Phase 2 aren’t necessarily guaranteed successful Phase 3 trials.
One reason some vaccines may fail in Phase 3 is that this stage of testing examines a larger and more diverse population than in Phase 2. All the scientists I interviewed mentioned this concern: Outcomes in a lab setting or a small clinical trial just aren’t always the same as in larger, more robust test populations.
That’s only one potential hurdle with a COVID-19 vaccine. Kelvin notes that the SARS-CoV-2 vaccine will face a challenge similar to our yearly influenza vaccine: providing protection from infection in both the upper and lower respiratory tract (the nose/throat and the lungs). The ideal vaccine will both prevent transmission by stopping viral replication in the nose and throat and also protect against serious disease due to viral replication in the lungs. That might be a tough combination to find. “Blocking infection in the nose is often a problem with vaccines that target respiratory viruses and are administered intramuscularly,” says Kelvin.
However, Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, has suggested that even a 50% effective vaccine is one he would “feel good” about in this case; we can’t let perfect be the enemy of good. After all, the flu vaccine tends to be 40% to 60% effective at preventing transmission each year, and it’s still absolutely essential for public health. A report in PNAS (Proceedings of the National Academy of Sciences of the United States) found that even if the flu vaccine were “only” 20% effective and only 43% of the population got it (which is around how many U.S. people get it each year), it would still prevent 21 million infections, 129,700 hospitalizations, and 62,000 deaths compared with no vaccine. The takeaway: Even a “less effective” vaccine can save a lot of lives and prevent a lot of illness.
When will a COVID-19 vaccine be available?
This is also still very much up in the air. (Seeing a pattern?) There are lots of ambitious estimates for this that, unfortunately, seem unlikely to come to pass.
President Trump has repeatedly suggested that a vaccine will be available in 2020, “maybe far in advance of the end of the year.” He has also suggested that the U.S. will have a COVID-19 vaccine before the upcoming election on November 3. Health and Human Services Secretary Alex Azar is a bit more reserved, recently saying, “We’ll have in the high tens of millions of doses of gold-standard safe and effective vaccine by the end of this year and many hundreds of millions of doses as we go into the beginning of next year.”
Even on our accelerated development timeline, many public health experts are wary of overpromising how quickly a vaccine will be available.
Kelvin says that “the October deadline to meet expectations of a COVID-19 vaccine in time for a November election seems tight.” She notes that for the majority of the lead vaccine candidates, Phase 3 clinical trials will be conducted over the next one to two years. Moderna is currently enrolling 30,000 volunteers for its Phase 3 trial, but that enrollment will likely last until late November, and researchers will need to follow up on participants for months after enrollment to see if the vaccine works and causes any significant adverse effects. And that’s the first vaccine to have reached this milestone—others lag behind Moderna’s timeline.
“Scientists have risen to the challenge and are compressing a process that usually takes a decade into a much shorter time period, but even with those efforts, virologists, vaccinologists, and immunologists understand that we have to actually analyze the human trial data to make sure a vaccine is efficacious and safe before it can be introduced to the general population,” says Morrison.
In a March article in The Journal of Infectious Diseases, a group of experts in science and ethics introduced a controversial proposal to further speed up these trials: deliberately infecting vaccinated people with SARS-CoV-2 during Phase 3 to more rapidly test the vaccine’s efficacy. The article’s authors say these trials “may subtract many months from the licensure process, making efficacious vaccines available more quickly,” thereby saving many lives globally due to the accelerated vaccine testing process. However, they note that this type of challenge study carries the risk of severe disease and even death for participants.
And, for this reason, none of the virologists I spoke with favored this suggestion. Rasmussen lists many cons and few benefits to this kind of COVID-19 challenge trial: “The risks to participants are huge, and even by mitigating those risks by only using healthy, low-risk volunteers and a low dose of virus, you would not get information about how a vaccine would work in people who are most at risk of developing severe COVID-19, such as older people or those with pre-existing medical conditions.” Kelvin agrees: “Due to the unpredictability of the outcomes of infection, I am of the opinion that the benefits do not outweigh the risks for human challenge studies and that these trials are not ethical at this time.”
What obstacles are we facing with distribution?
Even once we know of a vaccine that’s safe and effective (or effective enough), distributing it will be a challenge for multiple reasons.
In addition to providing funding to support the development of the vaccines themselves, Operation Warp Speed is reportedly working to decrease logistical hurdles to vaccine distribution. OWS is funding contracts for the production of syringes for vaccine administration and glass vial production for vaccine storage and transport. Globally, the Gates Foundation and Gavi, the Vaccine Alliance, are also working on vaccine distribution policies and logistics to identify and fill gaps for low- and middle-income countries.
Depending on the type of vaccine that we end up with, there might be additional challenges to overcome. Some vaccines need to be kept very, very cold as they pass through the whole supply chain, for instance, which will be a challenge for distribution to certain places, like rural areas, explains Rasmussen.
Then there’s the issue of cost. While it’s expected that insurance companies will cover vaccination at no cost to recipients, that is not yet set in stone. In the U.S., that will depend on approval by the Advisory Committee of Immunization Practices (ACIP). Where adults will receive vaccines is another pressing distribution question: At their workplaces? Local clinics? And will we need one dose or two? That can only be determined by following vaccine recipients over time.
Who should get a COVID-19 vaccine first?
When a vaccine is finally approved and a distribution plan is in place, it is unclear who will be first in line for doses. Kelvin notes that the World Health Organization (WHO) has established a Global Allocation Framework for COVID-19 products, which outlines priority groups as well as strategies for determining these groups, and within the United States, ACIP has also developed a COVID-19 vaccine prioritization plan, which is based on the influenza pandemic vaccine prioritization plan.
Priority groups identified to date include people at increased risk for severe COVID-19 (such as those with pre-existing conditions or advanced age) and essential workers, including health care personnel. It’s likely these groups will have first priority for vaccination, followed by the general public.
However, Rasmussen notes she is uncertain there is a clear plan “to ensure equitable access for marginalized communities disproportionately affected by the pandemic.” The pandemic is already highlighting racial disparities in access to testing, care, and treatment, and is consequently devastating Black and brown communities in the U.S. Vaccine access is likely to be another area fraught with inequality if there aren’t policies in place to counter these disparities.
Will enough people even use the vaccine?
Once the vaccine is eventually released, the natural next concern is: Will people get it? The vast majority of public health experts who do infectious disease work day in and day out certainly will. “Assuming the vaccine meets the FDA’s standards for safety and efficacy and is supported by data, I will get the vaccine as soon as I am able, and so will my family. I’m not encouraging people to do something I wouldn’t do myself,” says Rasmussen.
Morrison urges trust in the scientists who are carrying out this research every day. “Scientists are doing their jobs, and honestly, I have not slept a full night since January trying to keep on top of everything,” she says. “Neither have other scientists who are committed to doing their best to get us out of this situation.”
With that said, studies have already suggested that hesitancy about this vaccine is high. A recent nationally representative Gallup news poll of 7,632 adults suggested that 35% of Americans would decline a coronavirus vaccine even if it were free and FDA-approved. Some misgivings may come from the framing of the race to the vaccine. Even though Dr. Fauci has clarified that, “Right now the FDA is not cutting corners, but they’re doing things in a much more rapid, expedited way,” the term “warp speed” can still make it seem as though the process will neglect safety in favor of speed. The fact that the U.S. government is making payments to COVID-19 vaccine manufacturers conditional on meeting certain timeline goals also appears to incentivize timing over safety.
“I worry a lot that Trump will pressure the FDA to issue an EUA [emergency use authorization] for a vaccine without evidence of efficacy,” says Rasmussen. She notes that, in the very worst-case scenario, the U.S. government releasing a vaccine to the public that doesn’t work or is not safe would be catastrophic, would result in millions of people being exposed to an infection they believe themselves protected against, and would undermine vaccine confidence and fuel anti-vaccine sentiment, which is already a big enough challenge to public health as it is.
How should we stay safe in the meantime?
While we’re all anxiously awaiting a safe, effective vaccine, we still need to continue protecting ourselves and our communities. Wash your hands frequently, and use hand sanitizer if you don’t have access to soap and water. Continue social distancing as much as possible (and take care of your mental health while you do): Minimize your trips outside your home, and wear a mask when you need to go out. Keep in mind that just because you’re attending a family gathering doesn’t mean you’re safe; these kinds of get-togethers are responsible for a number of outbreaks, so mask up and distance from anyone you don’t live with, even family.
Finally, unfortunately, a vaccine won’t be a panacea. If a vaccine is only 50% effective and only 70% of the population agrees to be vaccinated, that likely will not be high enough to reach herd immunity levels, meaning the virus can continue to circulate among communities. Because of this and the other issues I’ve explored above, Rasmussen urges people to manage their expectations, as tough as that may be. “When a vaccine is approved, it won’t be immediately available and it won’t immediately end the pandemic. We will likely have multiple vaccines that will take time to distribute, along with the time it will take to win hearts and minds for public health,” she says. “A vaccine will be the beginning of the end, but that end will be measured over months or even years, not days.”