Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
On Sunday evening, Kathrin Jansen was watching the sun set on the banks of the Hudson River in upstate New York with her husband when the head of Pfizer, Albert Bourla, phoned her cell with the update she eagerly awaited. Jansen, who heads vaccine R&D at Pfizer, had learned that morning a massive placebo-controlled trial of the company’s candidate COVID-19 vaccine had a positive efficacy signal, but it wasn’t clear just then how strong it was. Bourla now told her that the trial’s interim analysis found that the vaccine, which uses a potentially revolutionary RNA technology, was more than 90% effective at preventing symptomatic cases of COVID-19. “This is unbelievable,” she told Bourla. Jansen and her husband began jumping up and down and soon had a champagne toast with “some really good stuff.”
The rest of the world joined the celebration today as Pfizer and its German partner BioNTech announced the encouraging results of their candidate in a press release. Pfizer says it could seek an emergency use authorization (EUA) for the vaccine from the Food and Drug Administration (FDA) in the next few weeks. But Peter Hotez, a vaccine researcher at the Baylor College of Medicine, speaks for many scientists when he says that despite the “apparently good news,” he would keep the champagne corked. “It’s always hard to read the tea leaves of a company press release,” without the underlying data, says Hotez, who also is part of a team making a vaccine against SARS-CoV-2, the virus that causes COVID-19. He stresses that whatever happens, the vast majority of the public will not have access to this or any other COVID-19 vaccine for several months. “This is a slowly evolving process,” says Hotez.
“There are a lot of unanswered questions,” adds Georgetown University’s Jesse Goodman, who formerly was chief scientist at the FDA and before that headed the vaccine division. Nothing, for example, is known about how long the immunity triggered by the vaccine will last, whether it can prevent severe COVID-19, and even whether it will slow transmission rates if it’s used widely in a population. It’s unclear how well it works in the elderly, who suffer the most from SARS-CoV-2. The vaccine, based on a simple strand of messenger RNA (mRNA), has to be kept at frigid temperatures of below 80 degrees Celsius to preserve the genetic material, and making and delivering it to hundreds of millions—if not billions—of people remain huge challenges.
Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases and a member of the White House’s Coronavirus Task Force, calls the data “very real” and “phenomenal.” But the pandemic “is not a light switch that you can turn on and off,” he says. “We still have to pay very close attention. Masks, social distancing, avoiding crowds, and hand washing–that is not going to go away, no matter how effective a vaccine is, because it’s going to take a while to get the country vaccinated to the point that you no longer are in an epidemic stage.”
BioNTech, a small German company working on mRNA vaccines to treat cancer, designed the COVID-19 vaccine and then partnered with Pfizer. Ugur Sahin, BioNTech’s CEO, says the companies tested more than 20 different stretches of mRNA coding for portions of spike, the SAR-CoV2 surface protein, which the virus uses to bind to human cells. They looked for mRNAs that were most likely to be taken up and expressed by dendritic cells, which “present” spike to the immune system to initiate antibody and T cell responses against the virus. “We spent a lot of effort in understanding what you need to get the vaccine into dendritic cells,” says Sahin. “That’s our key differentiator.” The BioNTech team then chose the mRNA that triggered the best immune responses in early human trials.
The subsequent efficacy trial, which has enrolled more than 44,000 people, quickly yielded results because of the skyrocketing number of COVID-19 cases in the United States, home to the vast majority of the trial’s 154 sites. The study design called for a Data Monitoring Committee (DMC) to unblind the data if 62 participants had symptoms of COVID-19 and tested positiv for SARS-CoV-2. Jansen says that on 3 November, the trial hit the 62 case mark and the companies started carefully combing through the still-blinded data to prepare it for the DMC to evaluate Sunday morning, by which time the trial had 94 people with COVID-19.
The company has not revealed precisely how many of those cases were in the vaccine versus the placebo group. So far, the trial has found no major safety problems. For safety reasons, FDA guidelines say that before a company can seek an EUA, two months must pass after at least half of the participants in a vaccine trial have received all of their doses. That point is about two weeks from now, and Pfizer anticipates that the trial by then will have reached its planned endpoint of at least 164 COVID-19 accumulated cases.
If Pfizer then files for an EUA as expected, FDA has promised to hold an open meeting of its vaccine advisory board—a step that committee members say is critical. “We all have a healthy skepticism because companies clearly want to sell their vaccines,” says Cody Meissner, a pediatrician at Tufts University School of Medicine who is on the committee and was nonetheless heartened by the positive report.
If the vaccine is formally deemed safe and effective or given an EUA by FDA and regulators in other countries, an ethical dilemma comes to the fore: whether to offer it to the participants in the study who received the placebo, which could compromise the trial’s ability to collect more data on the durability of its immune response and safety. Other COVID-19 vaccine trials might also be compromised: Participants might drop out if they had access to a 90% effective vaccine. “It could have a huge impact,” says bioethicist Christine Grady of the U.S. National Institutes of Health, noting that fighting the pandemic may require multiple vaccines, with known strengths and weaknesses. “Unless we have good data, that’s going to be a hard question to answer.”
Pfizer/BioNTech developed their vaccine without help from the U.S. government’s Operation Warp Speed, a massive effort to fast-track R&D of COVID-19 vaccine candidates, although the companies did agree to sell the government 100 million doses. Pfizer has cut deals with several other countries as well. Each person requires two doses, and Pfizer/BioNTech have produced only 500,000 doses, although they expect to have 50 million by the end of the year. By 2021, the companies project that they can produce 1.3 billion doses.
Still initial supplies will be severely limited even in the United States and they will remain short for most of the world next year. “If I look at the dose projections for 2021, and I look at what’s now been spoken for in bilateral deals around the world, it creates a fair amount of anxiety,” says Nicole Lurie, who works on COVID-19 vaccines for the Coalition for Epidemic Preparedness Innovations, a nonprofit that aims to improve equity and access to all countries. The need to transport and store the vaccine in ultracold conditions adds to the delivery headaches.
Nearly 50 other COVID-19 vaccines are in clinical trials; 9 of those have reached the efficacy phase. Seth Berkley, who heads Gavi, the Vaccine Alliance, says the positive data from Pfizer/BioNTech bode well for the many other vaccines that also rely on the SARS-CoV-2 spike protein, some of which don’t need ultra-cold storage. It is also an encouraging sign for other vaccine candidates using mRNA—one of which, from Moderna, could also have efficacy data this month.
Lawrence Corey, a vaccine researcher at the Fred Hutchinson Cancer Research Center who heads a U.S. network that’s testing several COVID-19 vaccines (but not the Pfizer/BioNTech candidate), says it’s an “amazing feat” that a vaccine has a clear efficacy signal just 11 months after SARS-CoV-2 was identified. “This is a revelation of science that we were able to do this,” says Corey.