Our First Preview of How Vaccines Will Fare Against Omicron
The variant will change the risk landscape for the vaccinated. The question is, how much?
And there it is, the first trickle of data to confirm it. In the eyes of vaccinated immune systems, Omicron looks like a big old weirdo—but also, a kind of familiar one. That’s the verdict served up by several preliminary studies and press releases out this week, describing how well antibodies, isolated from the blood of vaccinated people, recognize and sequester the new variant in a lab. The news is … well, pretty much the middling outcome that experts have been anticipating for weeks: a blunting of a certain type of immune protection, but not an obliteration.
Omicron harbors more than 30 mutations in its spike protein, the primary target of most of the world’s COVID-19 shots. And it’s certainly dodging some of the antibodies that vaccines goad our bodies into producing—more so, it appears, than the variants that have come before it. But the variant isn’t stealthy enough to elude the gaze of all antibodies we throw its way. Which likely means that a decent degree of vaccine-induced protection, especially against severe disease, will probably be preserved.
This is, in other words, “not great, but not the worst-case scenario either,” Vineet Menachery, a coronaviroloigst at the University of Texas Medical Branch, told me. Omicron’s likely to cause some degree of inoculation chaos in the coming months—more vaccinated people will probably contract the variant and, even, get sick. But Omicron hasn’t rewound our immunological clocks to the beginning of the pandemic. Menachery and other experts remain hopeful that there’s a path forward. If immunity is, in part, a numbers game, then boosters—and the additional antibodies they coax out—may help cushion the Omicron blow, at least for a time. A press release from Pfizer this morning seems to point to this possibility, though the company has yet to release its data to the public.
These new studies, which haven’t yet been published in scientific journals, are merely the beginning of a long and complicated conversation. In the coming days, the world will be inundated by a flood of similar laboratory data; nearly all of the findings will show a notable drop-off in antibody potency against Omicron, compared with the variants that came before. But the magnitude of the blunting will vary from study to study—as already seems to be happening—and it’ll take time to reach consensus. It’s way too early to actually, qualitatively assess how much Omicron will chip away at vaccine effectiveness, which encapsulates a lot more than what antibodies alone have to offer, and hinges on how well immunized people actually fare against the variant.
Immune systems are complex; so is the real world. Even so, these early reports mark our first concrete indications that Omicron is rejiggering the risk landscape for the vaccinated. It’s not because the shots themselves have changed, or even the immunity they’ve left behind. It’s because we’ve yet again allowed our foe to morph into something more formidable.
To find our footing with this new glut of evidence, it’s worth taking a step back to understand how the data came about—and what they can and cannot tell us. The results we’re seeing now are primarily the product of neutralization assays, laboratory-based experiments that slurry together Omicron (or an artificial look-alike) with antibodies sampled from the blood of people who have been vaccinated or infected, and see if the molecules can block, or neutralize, the pathogen before it infiltrates cells. What researchers observe with these studies isn’t an exact approximation of what goes on in a complex human body. But when they need answers fast, a neutralization assay can serve as a decent bellwether for whether our bodies’ frontline immune protection might hold up, Lisa Gralinski, a coronavirologist at the University of North Carolina at Chapel Hill, told me.
A neutralization assay was the driving force behind a widely discussed study posted online this week, led by the virologist Alex Sigal of the Africa Health Research Institute, in South Africa, one of the first countries to detect and report Omicron’s existence. The researchers gathered blood plasma from 12 people who’d received Pfizer’s vaccine, six of whom had also previously been infected by an older SARS-CoV-2 variant, a near-perfect match for the version of the virus that the shot had been modeled upon. The antibodies, on average, neutralized the older variant about 41 times better than they neutralized Omicron. The researchers didn’t do a head-to-head comparison between Omicron and other variants of concern, but similar studies have found that vaccine-elicited antibodies are roughly three to 15 times worse at neutralizing Beta, another coronavirus variety with a wonky-looking spike, than the original SARS-CoV-2.
The outlook on Omicron, then, can seem bleak: It is trickier for antibodies to glom on to and quell this virus, compared with the variants that preceded it. But the case on Omicron immunity isn’t closed yet. For one, 41 might not be the be all and end all, though it may be quite close, based on other data now being shared. Other researchers, collecting blood from other populations with diverse infection histories or ages, or who received other vaccine brands at different points in time, might see somewhat disparate numbers. Omicron is still relatively scarce in most parts of the world; scientists need time to track it down, then grow it.
In the meantime, some might try a workaround: cobbling together a fake Omicron pseudovirus that’s been harmlessly engineered to display the variant’s version of the spike protein. Another research group at the Karolinska Institute, in Sweden, has already done this and posted its own preliminary results, which also surveyed a small group of people, some of whom had been both infected and vaccinated. The Swedish team’s estimates for the drop in neutralization weren’t nearly as drastic—about five- to sevenfold lower for Omicron. But a lot of their participants were health-care workers who had been repeatedly exposed to the virus; some had been boosted. And other experts advised a little more caution when interpreting studies that used faux-Omicron copycats, which might not always behave like the real thing.
Pfizer’s preliminary studies, too, have relied on pseudovirus; the company today reported an average of a 25-fold drop in neutralization in 20 people who’d received two doses, according to company spokesperson Jerica Pitts. Experts told me they were more inclined to stick with the 40-ish number until we know more. That drop may sound dire, but “it’s not a complete wipeout,” Penny Moore, a virologist at the University of the Witwatersrand, in South Africa, who worked with Sigal on his study, told me. Most people should still have some vaccine-trained antibodies around that can cling to the parts of the spike that Omicron didn’t modify.
The laboratory data also represent a single snapshot in time—the moment when blood was taken out of a vaccinated person. But the antibodies in our blood currently aren’t the ones we’re stuck with forever. The point of a shot isn’t to keep bodies flush with gobs of antibodies in perpetuity; it’s to endow them with the ability to produce more of them when they’re needed. It’s why antibody levels naturally drop after immunization, and why they rocket back up when people get infected. Within days of exposure to Omicron, Menachery told me, “we’ll be talking orders of magnitude more protection.” The capacity to churn out antibodies, in particular, is holstered in B cells, which seem to stick around in droves after vaccination, and continue to sharpen their responses to spike for months. (It’d be a different story if there was no preexisting antibody pool to amplify—which is not the case among people who have been vaccinated.)
Neutralization assays also can’t capture the performance of other immune defenders. Some antibodies can’t neutralize viruses on their own, but can still detain them with the help of other immune fighters—a tag-team approach that a neutralization assay won’t capture. Also essential to most antiviral responses are T cells, calculating mercenaries that help B cells pump out antibodies, or blow up virus-infected cells. T cells can’t prevent infections on their own, but their power is in their flexibility. Variant mutations that would totally bamboozle antibodies can’t always fool T cells, which means a lot more of them will be fairly Omicron-proof, Gralinski told me. Pfizer’s press release tentatively confirms this.
All of this means that a 40-fold drop in neutralization wouldn’t suddenly make our COVID-19 vaccines perform 40 times worse, especially against the most serious outcomes. Again, we still don’t have solid data on vaccine effectiveness. When the shots’ protection ebbs, it tends to do so stepwise: first, against infection, then transmission and symptoms, and finally against severe disease. High antibody levels are generally a good sign; when the body’s chock-full of the molecules, they form a blazing frontline defense, sometimes capable of blocking infection entirely. But having diminished antibody levels isn’t all that telling, because other immune fighters might jump in to compensate when a virus invades. Even in a worst-case scenario, where protections against infection and mild illness substantially fray, Deepta Bhattacharya, an immunologist at the University of Arizona, told me that vaccine effectiveness against severe disease probably wouldn’t suffer more than “a small drop.”
Right now, the road ahead is muddy. For weeks, vaccine makers have already been gearing up to revamp their recipes to better accommodate Omicron; Pfizer, for instance, expects it could have an Omi-vax available by March. But experts aren’t yet ready to take this week’s data as a surefire sign that we’ll need to go down that path—just that it remains wise to prepare. Over the next few weeks, they’ll be monitoring not just how Omicron interacts with antibodies but also how deadly the virus is, and whether it seems poised to usurp Delta’s global throne. If Omicron fizzles out on its own, or doesn’t land tons of people in the hospital, another vaccine formulation might not be necessary, even if our current shots aren’t its exact Achilles’ heel.
In the meantime, a viable, if imperfect, stopgap is available to millions of people, at least in well-resourced countries, where supplies of COVID vaccines abound—booster shots. Pfizer’s press release pointed to a pattern that researchers have been hoping to see for weeks: Some vaccine-trained antibodies are clearly bad at sticking to Omicron’s outsides, but if there are enough of them around, they can still collectively bring the virus to heel. The antibodies the researchers pulled out of people doubly dosed with Pfizer were, on average, 25 times less able to neutralize an Omicron look-alike in the lab. But the company also found that a third dose rocketed Omicron neutralization levels up by a factor of 25, suggesting that quantity might at least partially patch holes in quality. A huge caveat: The jury’s still out on how long that antibody bump lasts. But the results are an encouraging echo of past data that have shown that boosters increase people’s ability to fight off all sorts of variants, not just the ones in the original-recipe shots.
The company’s report seems to match up well with the data out of South Africa. People who had been infected by SARS-CoV-2, then vaccinated, had far more neutralizing antibodies at baseline—an observation that’s been made before, and termed a sort of super-powerful “hybrid immunity.” Those sky-high levels provided a buffer against Omicron’s stealth: There was still a big drop in the antibodies’ ability to neutralize the variant, compared with the earlier strain. But where they landed wasn’t all that bad. “The higher you start, the better off you are,” Moore said. “And there are many ways to get there.”
That said, boosters are no panacea. They can’t be expected to fully erase Omicron’s setbacks, and the new variant will still evade booster-borne antibodies better than its predecessors did, as evidenced by a study out of Germany. We could still end up needing a bespoke Omicron shot, or something much like it. That might be wise even if Omicron doesn’t turn out to be a significantly worse threat, considering that the variant the vaccines were modeled on was displaced long, long ago by its more transmissible successors. That said, making something hyper-specific to Omicron might not be a perfect solution. We’d have to make sure it still worked well against other variants, including, for the foreseeable future, Delta, which is still the globe’s dominant variant.
Boosting with the shots we already have, then, feels more urgent now than ever. That’s a problem, unfortunately, in a world where vaccine distribution has been patchwork at best, leaving billions without first doses while those in wealthier countries help themselves to thirds. “Right now we should be prioritizing getting people some immunity,” Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital in Memphis, told me. Initial inoculations remain essential to ensuring that people around the world have a baseline immune response to build on, and won’t be facing off with Omicron entirely unguarded. Where we fail to vaccinate widely, the virus will find more inroads; where the virus finds more inroads, more variants will certainly arise.