There’s one thing that doctors, scientists, researchers and government officials all agree on: we don’t yet have enough Covid-19 vaccines for the U.S. population. How to use the vaccines we do have, however, is where the disagreement starts. Under threat from an ever-worsening surge of cases and a new, more highly-transmissible variant of SARS-CoV-2, some researchers have suggested an unorthodox approach: instead of limiting the two-dose mRNA vaccine regimen to those most at-risk, give everyone possible the first dose of the vaccine so that more people have at least some level of protection against Covid-19.
This idea is rapidly gaining support among researchers and policymakers, who argue that it’s better to get more protection sooner. Other scientists – and the FDA – caution that the evidence to support the idea of delaying the second dose is not only thin, but risks making the pandemic worse.
“It’s something that I would not have favored two weeks ago,” says Bob Wachter, chairman of the Department of Medicine at UCSF, but several things have recently changed, he says: The U.S. is battling a tremendous surge in cases, with almost 200,000 new cases of Covid-19 per day and more than 128,000 Americans currently hospitalized. In addition, the good news of two emergency authorizations for mRNA vaccines has been quickly overshadowed by a slow and confusing rollout. Finally, a more contagious version of the SARS-CoV-2 virus has been found in several states. During an emergency situation like a pandemic, Wachter says, “all things should be on the table.”
Wachter isn’t the only expert who supports the idea of delaying the second dose of the vaccine. On January 5th, three papers and a commentary published in Annals of Internal Medicine from researchers at Yale, the University of Washington, Fred Hutchinson Cancer Center, and Stanford University all suggested that more deaths could be averted by immunizing a large percentage of people with the first dose of an mRNA vaccine compared to waiting to roll out the full two-dose regimen.
One big unknown surrounding this idea, though, is that it’s not exactly clear how much immunity a single dose of the Pfizer-BioNTech or Moderna mRNA vaccine really provides. In materials submitted to the FDA for review, both companies found that the vaccines were about 95% effective at preventing severe cases of Covid-19 after two doses. But graphs from both trials also suggested that about about two weeks after getting the first dose of the vaccine, people who were vaccinated were less likely to contract Covid-19,even before receiving the second dose. The efficacy of the first dose by itself turns out to be slightly above 50% for both vaccines, though it is not known how long this protection lasts, since all participants in the study got both doses on time.
A lack of evidence is what some researchers, and the FDA, are citing for their reluctance to endorse the first-dose strategy. A single dose of the vaccine “may provide protection,” says Scott Hensley, an immunologist at the University of Pennsylvania, but “in my opinion it’s just reckless to try and just do that experiment out there in the world.” Instead, the companies that created the vaccine should be studying this issue in rigorous clinical trials. Stephen Goldstein, an evolutionary virologist at the University of Utah, agrees: “I wouldn’t do it without a trial under any circumstances,” he says.
Though anecdotes aren’t data, there’s some high-profile reason for caution. Two members of Congress, Rep. Kay Granger and Rep. Kevin Brady, have tested positive for Covid-19 after receiving their first dose. There are other notable examples of this occurring, though without a clinical study it’s impossible to say how typical these cases are.
On January 4th, the FDA released a statement echoing concerns about the limited amount of evidence on the effectiveness of a single dose of the vaccines. “Suggesting changes to FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence,” the statement says.
Several scientists who spoke with Forbes for this story, including Goldstein, emphasized that even if one dose of the vaccine prompts an immune response, we have no idea how protective that immune response may be — or how long it might last. “That second dose seems to be important to getting really high potency neutralizing antibodies,” Goldstein says, referring to the special type of antibodies that are tasked with defending cells from Covid-19.
Another potential concern about delaying the second dose is that a single dose of the vaccine could cause new, more dangerous strains of SARS-CoV-2 to emerge. When someone is only partially immune, Hensley says, their bodies won’t prevent the virus from replicating. In fact, the virus could replicate in a way that it actually mutates to evade the vaccine in the future. While this is a concern, Hensley says, it is still only a theory. However there is already one SARS-CoV-2 variant, the 501.V2 variant that was first identified in South Africa, that has mutations that may render the currently authorized vaccine less effective.
When asked if the company plans to conduct new trials to study the effectiveness of one dose of its vaccine, a spokesperson from Moderna said, “At this point we wouldn’t have any further information to share about any potential ongoing regulatory discussions, which would precede any future clinical trials.” A spokesperson from Pfizer similarly did not say whether the company planned a new trial, but did note that “although partial protection from the vaccine appears to begin as early as 12 days after the first dose, two doses of the vaccine are required to provide the maximum protection against the disease.”
Despite statements from the companies and the FDA, Wachter, the UCSF physician, says he has no patience for people arguing that we should just stick to the initial plans. “There’s nobody arguing about not giving the second dose,” he says, just that the second dose should be delayed until more people can get at least the first dose. In his, and many others’, view, the potential risks are worth the reward. “Often you have to make decisions in a pandemic, and in life, without complete information,” he says.