Barely a year after vaccine developers reported spectacular successes against SARS-CoV-2, the latest variant of the virus has presented them with a new challenge. Omicron is spreading at unprecedented speed, and studies of blood samples and emerging real-world evidence show one reason is its ability to dodge immunity, whether from previous infections or vaccination. The new threat has galvanized vaccine developers and public health officials—but they are not all pushing in the same direction.
Reacting to evidence that an additional dose can restore some protection against Omicron, many countries are racing to give booster shots of existing vaccines. Some scientists think that is unnecessary, arguing two doses of the current messenger RNA (mRNA) vaccines will suffice to keep most people who are otherwise healthy from getting seriously sick with COVID-19. Others think it’s time for revised vaccines. A booster tailored to Omicron would likely offer better protection, vaccinologist Florian Krammer of the Icahn School of Medicine at Mount Sinai told Science earlier this week, and vaccine manufacturers, eyeing a new market, are doing the preliminary work to concoct new formulations.
Yet another camp has embraced a bolder option. Rather than chasing SARS-CoV-2 variants with tailored shots, they say it’s better to push harder for universal coronavirus vaccines that would aim to protect against every new mutant of SARS-CoV-2, as well as other coronaviruses that nature might throw at humans in the future. Because of Omicron, “There is even stronger interest in our approach,” says Kayvon Modjarrad of the Walter Reed Army Institute of Research, who is spearheading the development of a pancoronavirus vaccine candidate that has just completed its phase 1 trial. Other pancoronavirus candidates may start their first trials in 2022.
The dramatic rise of the Omicron variant, which already accounts for almost half of all cases in some countries, has brought a broader debate to a head: how to handle future COVID-19 waves as we move further down the Greek alphabet of SARS-CoV-2 variants. “The idea of reboosting every 6 months or even every year, that’s not a public health strategy,” says Céline Gounder of New York University’s Grossman School of Medicine, who was a COVID-19 adviser to President-elect Joe Biden during the transition.
Paul Offit, a pediatrician at the Children’s Hospital of Philadelphia, contends it’s “extremely unlikely” Omicron will make healthy, vaccinated people under age 65 very sick because it can’t outfox T cells—which early studies suggest are largely unaffected by this variant’s mutations—and immune memory. The current vaccines, he notes, have shown 90% or better protection against severe disease, “as defined by the likelihood of having to visit a doctor, go to the hospital, or worse,” he says. In expecting SARS-CoV-2 vaccines to protect against transmission as well as mild and moderate disease, “we’re holding this vaccine to a different standard,” Offit says. He doesn’t think giving booster shots to entire populations—as most countries that can afford it are now doing at breakneck speed—is necessary, even in the face of Omicron.
Gounder, though, argues a booster push currently makes sense because there are so many unknowns about Omicron’s severity. “Let’s give third doses right now to buy us some time while we sort it out,” she says.
For now, the booster efforts rely on the same formulations and doses that were authorized before Omicron arrived. But Moderna, which received authorization from the U.S. Food and Drug Administration (FDA) to cut its current dose in half for the third booster shot of its mRNA vaccine, is examining the impact antibodies have against Omicron in a new clinical study of a full-dose booster. It and other developers are also creating variant specific updates of the currently authorized vaccines—which all are derived from the original SARS-CoV-2 that circulated in Wuhan, China, in early 2020. Moderna and the other producer of a widely used mRNA vaccine, Pfizer and its partner BioNTech, say they could begin to deliver an Omicron-tailored vaccine as soon as March 2022. But they warn that shifting to a new vaccine inevitably would cut production of the current one.
Moderna has tested the impact of mRNA mixtures that combine the original variant’s spike with new ones, and suspects this might provide broad enough protection to counter Omicron. Pfizer and BioNTech reported last week that in a clinical trial, a boost with an mRNA vaccine coding for the spike of an earlier variant, Alpha, elicited neutralizing antibody levels against Omicron more than four times higher than boosts with spikes from Beta, Delta, or an Alpha/Delta mix. “The Omicron variant shares multiple mutations with the Alpha variant,” explained BioNTech’s CEO, Uğur Şahin, at a press briefing.
No Omicron vaccine has yet entered clinical trials. Regulatory hurdles also remain unclear: Will FDA or other regulatory bodies simply accept evidence of immune responses correlated with protection rather than clinical proof of efficacy? Although studies have shown neutralizing antibodies correlate with protection, other immune responses clearly play major roles: An analysis of the large Moderna vaccine efficacy trial found neutralizing antibodies accounted for only 68% of the protection. Still, Peter Marks, who heads the vaccine division at FDA, says, “immunogenicity studies based on neutralization assays will suffice for a change if we need it.”
Immunologist John Moore of the Weill Cornell Medical College, who favors boosting as many people as possible with the current mRNA vaccines, calls it prudent to do the preliminary work on Omicron-focused vaccines, but suggests by the time they’re scaled up, they may not matter. “The Omicron wave may be over by March,” he says.
“Maybe we are too late for the first wave, but if Omicron is here to stay, we need a specific vaccine,” Krammer counters. “I think not acting is problematic.”
Moore also remains wary of companies, which could benefit financially if variant boosters are deemed important, steering vaccine policy. “It is going to have to be based on as much data as possible, and some very serious discussions in the high levels of the administration, without the company execs putting their finger on the scales,” he says.
Nicole Lurie, who heads the U.S. division of the nonprofit Coalition for Epidemic Preparedness Innovations (CEPI), also sees no need for an Omicron-specific vaccine given the transmission rates, but says the companies should be prepared to make vaccines for future mutants that move more slowly. “Or they have to get faster at making vaccines,” she says.
Lurie and others say Omicron has underscored the need for vaccines that protect against all severe acute respiratory syndrome (SARS)-related viruses—known collectively as sarbecoviruses—or, better yet, all viruses in the coronavirus family. CEPI in March put out a call for proposals to develop such vaccines, hoping to put $200 million toward such projects over the next 5 years. The U.S. National Institute of Allergy and Infectious Diseases (NIAID) in September announced three new grants totaling $36.3 million to university research teams that have the same goal. “It’s a compelling need,” says NIAID Director Anthony Fauci, who is co-author of a perspective on pancoronavirus vaccines in today’s issue of The New England Journal of Medicine (NEJM). And he hopes NIAID will receive additional funding to support more pancoronavirus projects. “I don’t want money given to me in dribs and drabs,” Fauci says. “I want it in the base so I can make a multiyear commitment to my investigators.”
A pancoronavirus vaccine may not be as tall of an order as it might seem, says Fauci, who takes heart in the fact that current vaccines based on the original Wuhan strain have powerfully prevented severe disease with all variants. “That bodes pretty well for the possibility of getting a pancoronavirus [vaccine] that you can boost with and protect against everything,” he says. Already, several have fared well in animal trials, and several candidates will start human trials next year.
Some vaccinated people may already have pansarbecovirus antibodies, a team led by Linfa Wang of the Duke-NUS Medical School in Singapore found. In work posted as a preprint 4 months ago and published on 7 October in NEJM, Wang’s team studied people who nearly 2 decades ago had recovered from SARS and recently received the Pfizer-BioNTech COVID-19 vaccines. In test tube studies, their antibodies neutralized SARS-CoV, which causes SARS, SARS-CoV-2, and several SARS-related coronaviruses found in bats.
Wang is now making a vaccine booster based on a hybrid of spike sequences from SARS-CoV and SARS-related bat viruses, but he doesn’t have access to monkeys to rigorously test the concept first. He’s also still shopping for a company to back the project. “Anything to do with commercial partners takes time,” Wang wrote in an email, explaining that he hopes to launch clinical trials in the first half of 2022. “The Omicron emergence will hopefully make this move a bit faster!”