In May, biotech company Moderna Therapeutics announced that it had just completed its first phase of testing a COVID-19 vaccine (mRNA-1273), and that said vaccine showed promise in protecting against the novel coronavirus. Since then, dozens of other companies and research institutions have announced their own attempts at making a coronavirus vaccine. Most recently, Pfizer announced that its vaccine appears to be 90 percent effective at preventing COVID-19 according to data from its clinical trials—far more effective than most scientists even hoped for. (The company’s clinical trials are still ongoing, and data has yet to be shared with the public.)

Given that SARS-CoV-2 (the specific coronavirus that causes the disease COVID-19) has infected over 50 million people worldwide and claimed over 1.25 million lives, the hope placed in a vaccine can’t be overstated. However, doctors warn that the question of when a Food and Drug Administration-approved version will be ready for public consumption remains unclear.

“A vaccine has to accomplish two things: It has to be safe and it has to be effective,” says Alan Rothman, MD, head of the University of Rhode Island’s Laboratory of Viral Immunity and Pathogenesis who’s studied viral diseases for over 25 years. “In this case, a vaccine that fulfills both these criteria will present no major side effects and will keep people from contracting COVID-19.” Meeting both of those standards will be a challenge for Moderna Therapeutics, Pfizer, and the host of other companies (like GlaxoSmithKline and Heat Biologics) diligently working to develop and test a vaccine.

Developing sound vaccines—like the ones we use to guard against HPV, measles, the flu, and more—is a marathon, not a sprint. Below, Dr. Rothman and Bryce Chackerian, PhD, a vaccine researcher at the University of New Mexico’s Comprehensive Cancer Center (who’s personally working on a COVID-19 vaccine) share everything they know about a viable timeline for the widespread use of a COVID-19 vaccine.

First of all, what’s the deal with the Moderna Therapeutics vaccine?

When your body first encounters an antigen—aka a foreign, harmful substance like bacteria or a virus—the immune system reacts by creating antibody proteins. These proteins attach to viruses and other foreign invaders and either destroy them or prevent them from spreading further inside of your body. These antibodies also “remember” the virus even after you’ve recovered, and will more quickly re-target it and fight it in the event it comes back.

However, many antigens are too powerful for the immune system on its own, which is where vaccines come in. Most vaccines work by injecting a person with a safe form of the disease in question—such as an inactive virus—in order to help their immune system learn to identify it and produce antibodies to it. Thanks to the vaccine, your body learns how to effectively fight off something that is otherwise super dangerous.

The Moderna Therapeutics vaccine currently being tested, called mRNA-1273, uses a slightly different type of vaccine called (you guessed it!) an mRNA vaccine. As the University of Cambridge explains, “Unlike a normal vaccine, RNA vaccines work by introducing an mRNA sequence (the molecule which tells cells what to build), which is coded for a disease-specific antigen. Once produced within the body, the antigen is recognized by the immune system, preparing it to fight the real thing.” Rather than injecting you with the antigen itself, this kind of vaccine gives your body the tools to make a key part of the antigen (in safe amounts) so your immune system learns what it is and exactly how to fight it off. Moderna’s vaccine is targeting the “Spike (S) protein,” which usually appears as red, tendril-like structures on pictures of SARS-CoV-2 and is the key mechanism behind the virus’s ability to attack your body’s cells.

This newish technology is exciting because RNA vaccines are easier to produce than other kinds of vaccines, says Dr. Chackerian. “That’s one of the reasons I think Moderna was able to actually move this vaccine into humans so quickly because the technology is so easily adaptable to new targets,” he says.

In early May, Moderna received an FDA Fast Track designation for its vaccine mRNA-1273, allowing the company to expedite the review of its study. The full study results have not been released, so the following is based on the company’s press release. Using mRNA technology, Moderna researchers divided 45 healthy people ranging in age from 18 to 55 into three small groups that received one or two shots of mRNA-1273 at three dose levels: 25, 100, or 250 micrograms. According to the company’s summary data, the first four volunteers to get the lowest doses and the first four to get the medium doses of mRNA-1273 have reportedly developed neutralizing antibodies that have been found to be able to fight SARS-CoV-2 based on a blood test known as a Plaque Reduction Neutralization Test (PRNT). (Other data from the other study participants has yet to be released or published in a journal.)

This is an extremely small sample of success, but scientists both inside and outside of Moderna are hopeful that this is step one in creating a vaccine that could one day save thousands—or even millions—of lives.

Here are more deets about how vaccines work, straight from a biochemist: 

What about the other vaccines being developed?

The potential vaccine currently making headlines comes from researchers at Oxford University and the drug company AstraZeneca. In a study published in The Lancet on Monday, the vaccine developers report that in their phase I/II clinical trial of over 1,000 people, their vaccine elicited an immune response in the form of increased antibodies and a T-cell response with only some minor side effects. Basically, this means that in response to the vaccine, subjects’ immune systems created antibodies to neutralize the virus itself, along with specific immune cells that can identify and destroy infected cells.

“Having both [immune responses] after vaccination—sometimes after a single dose, but much better after a second dose—is pretty encouraging,” Oxford professor and study author Adrian Hilltold NPR.

The vaccine, called ChAdOx1 nCoV-19, is made using a modified form of a virus that causes the common cold in chimpanzees. Per the BBC, this particular virus was manipulated so that it contained the above-mentioned spike proteins the novel coronavirus uses to infect healthy cells—allowing the body to learn how to fight off those proteins without getting sick. (Reported side effects include muscle aches and chills, per NPR.) However, the trials were paused briefly in September after a participant became seriously ill. The trials resumed in October.

The Lancet also published clinical trial results for another vaccine from Chinese pharmaceutical company CanSino. This phase two trial found that the company’s vaccine elicited an immune response that could neutralize a SARS-COV-2 infection in most of the 500 participants. However, per StatNews, there’s some evidence that the vaccine doesn’t work as well in specific people, including people older than 55—problematic since older adults are more vulnerable to complications from the coronavirus.

How promising are these vaccines, exactly?

These studies and results are just the beginning of the vaccine process. “This is a phase one study,” says Dr. Rothman of the Moderna vaccine results. “The purpose of phase one studies is not to figure out what vaccine is going to be effective; the purpose is to make sure that it’s safe to give to other test subjects. So when you only have given it to a few dozen individuals, that isn’t really very much to go by.” Dr. Chackerian agrees, going so far as calling this phase the “safety” phase. The mRNA-1273 vaccine (as well as the others mentioned above) will have to undergo two more intense phases of testing under the careful eyes of those at the FDA and other regulating bodies.

In Dr. Chackerian’s mind, there are two more reasons to approach any newborn vaccine with a critical eye. First and foremost, we don’t yet know how valuable having these SARS-CoV-2 antibodies actually will be when it comes to safeguarding an individual against this particular virus. The scientific community has discussed antibodies ad nauseam in recent months, but they’re really just one way to gain immunity. Right now, researchers and doctors aren’t convinced they’re the best way. “Antibodies are just one part of an immune response that can protect you—and they’re quite important because most vaccines work by inducing antibodies—but there are some other components of the immune response that could also be valuable at providing protection from infection,” says Dr. Chackerian.

Beyond that, Dr. Chackerian says that even if antibodies do become the primary way to combat COVID-19, researchers aren’t sure how long those antibodies will stick around to protect the body. “This is the same issue we run into with people who’ve recovered from coronavirus. It appears that most of the evidence is that those people seem to be protected from infection after they’ve recovered, but we don’t know how long that protection is going to last for. That’s just something that we’re going to have to see over time,” says Dr. Chackerian.

Similarly, not every type of vaccine provides the same amount of immunity for the same amount of time; it depends on the disease itself, and other factors. “Some vaccines are really good at eliciting very long-lived antibody responses,” says Dr. Chackerian, such as the measles vaccine, which has a half-life of 3,000 years (meaning that you would basically be immune for 3,000 years…if you could live for that long.) “Other vaccines are less good at doing that, so the antibodies go away much faster.” In the case of Moderna’s early-stage vaccine, scientists just don’t yet have the data to know how long the immunity will last.

Why are phase two and phase three of vaccine testing so important?

Fortunately, the concerns about Moderna’s mRNA-1273 test (as well as those of other vaccines being tested and developed) have the opportunity to be assuaged once the researchers proceed to stage one and stage two of developing the vaccine. The FDA’s Center for Biologics Evaluation and ResearchExternal (CBER) carefully monitors and approves all three phases of developing any vaccine.

Phase two and phase three test the existing vaccine on more of the right demographic of people and over longer periods of time. “Moderna got some adjustments from their phase one trial. So the next step in phase two, of course, is to now test the vaccine in more volunteers, and to look more carefully at the immune responses that are induced in patients who have gotten these doses that were based upon as a result of the phase one trial,” says Dr. Chackerian. This will look like not only a larger sample size, but one that’s representative of those most at risk for experiencing serious symptoms of the virus, such as older people and those with pre-existing conditions or compromised immune systems. Then phase three will take the vaccine that was finessed in stage two and test it on a massive sample size of thousands of people to confirm its safety.

Dr. Rothman says that phase one and phase two in particular present a vital trial period for determining if the vaccine has any risky side effects. For example, when researchers first encountered what we now know as swine flu in 1976, they overlooked one side effect of their swiftly-created vaccine. “Under Gerald Ford, the U.S. government ramped up production very rapidly of a vaccine against the new strain of influenza. It followed the same typical injectable influenza vaccine, and it wasn’t until they started using it widely that they found a very rare side effect associated with that vaccine called Guillain–Barré syndrome, which can be a very serious neurological problem,” he says.

The whole world has such an urgent need for a COVID-19 vaccine, Dr. Rothman and Dr. Chackerian say that it’s vital for both the scientific community and the watchdog government bodies like the CBER to look at this vaccine under a microscope. That’s why the World Health Organization (WHO) and the President of France, the President of the European Commission, and the Bill and Melinda Gates Foundation recently hosted an event for other world leaders to establish a plan for global access to the vaccine. The WHO has also led the charge to develop and test vaccines, standardize testing procedures, and decide what demographics should be represented in order to adequately test the vaccine. With the U.S. officially leaving the organization in June 2021 (an announcement President Trump made last month), it’s unclear how that will affect American efforts to develop and test a vaccine.

When’s the soonest we might see the vaccine?

Both doctors say that placing a timeline on the COVID-19 vaccine is a near-impossible task. Not only do we still have to get through a few more phases of the clinical trial itself, but there are also a lot of hoops developers like Moderna have to jump through before there’s a vaccine on the market. The FDA still has to review the literature surrounding the final vaccine and approve it, then the vaccine has to be manufactured, quality-tested, and distributed around the country.

As past vaccine development tells us, that timeline from research to final approval really varies. “Researchers on the HPV vaccine published lab-based work in the very early 1990s, and then the vaccine was approved in 2006. It took about 15 years for the vaccine to go from discovery to something that was actually approved by the FDA,” says Dr. Chackerian. Meanwhile, he says the mumps vaccine took only about four years to develop in the 1960s.

That said, the federal government has emphasized the importance of having a viable vaccine ASAP, and have fast-tracked the testing and approvals process to facilitate development. “We hope that by end of this year, or the beginning of 2021 we will at least have an answer whether the vaccine or vaccines—plural—are safe and effective,” said Anthony Fauci, MD, the director of the National Institute of Allergy and Infectious Disease in a recent Facebook Live conversation hosted by the National Institutes of Health (NIH).

Dr. Chackerian feels hopeful that vaccination technology has improved enough in the last few decades that we may be able to see more rapid production. “I’m actually very optimistic that this vaccine can be approved faster. The vaccines that we’re using today clinically are very, very safe and we’re equipped to address worries about safety pretty easily,” he says. Plus, he believes the seriousness of the pandemic has created a lot of urgency for developers and regulators to get something ready sooner rather than later. He feels hopeful that a vaccine could be developed faster than the 12-to-18 month prediction that’s been circulating in the news.

Dr. Rothman, on the other hand, approaches the timeline with a bit more skepticism. For him, the best-case scenario is ramping up (safe) testing of the Moderna vaccine and any others that may make it past phase one in the summertime, so that they’re ready to be tested en masse if the world experiences a second go with COVID-19 in the fall (a possibility that hugely concerns health experts). “We need to have the [phase three] study set up in a place where there is enough infection going on at that time to collect information about protection. If, as many people suggested, we experience a second wave of COVID in the fall, we probably want to be ready to do that study then collect information,” Dr. Rothman says. Should that happen, he thinks the earliest a vaccine could be approved is in spring or summer 2021—but will likely be later than that, in his opinion.

In short: There’s no crystal ball to reveal how and when the world will recover from the large-scale human tragedy we’re currently living in. It’s important to remember that 23 companies in the United States alone have pivoted their daily operations to seek a vaccine or treatment options for this virus. And if history’s any indication, one of them will find one.

This story was originally published on May 21, 2020. It was updated on November 9, 2020.