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Animal studies: Omicron-specific boosters don't work any better than current boosters against Omicron

AP Photo/Ben Gray

I can’t decide if this is good news or bad news.

The reason it’s bad news: Omicron now accounts for 100 percent of COVID cases in the U.S., according to the CDC. No typo. If the new variant is the only game in town, it sure would be nice to have a vaccine that works especially well against it. But if this (very small) study of macaques is any indication, we’re out of luck. Macaques who got three doses of the original vaccine did as well against Omicron as those that got two of the original vaccine plus one of the new Omicron-specific shot.

The reason it’s good news: In the study, both the original booster and the new bespoke booster worked darned well against Omicron. If we already have a shot on hand that does as well against the variant as a new vaccine developed specifically to combat it, that’s … a good thing, no? It’s already on the shelves! Moderna doesn’t need to upend its entire manufacturing line to switch over from making one type of product to a different type.

Importantly, [both types of] boosters … had a positive effect on memory B cells, which are responsible for cranking out antibodies to fend off a virus. Both the original vaccine and the updated jab prompted a rise in the animals’ levels of ‘cross-reactive’ memory B cells — those that target many variants, not just the one in the vaccine.

“For now, that’s a very good thing,” says Robert Seder, a co-author of the paper and an immunologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “It means we’re still able to cover all known variants with a boost” of the current vaccines. However, he cautions that the study only examined immune responses up to four weeks after the boost, and says that it is not clear how long the increase in antibody production will last.

Seder’s group also exposed animals boosted with either the original vaccine or the Omicron-matched version to Omicron. “Either boost completely shut down viral replication within two days,” he says. In both this experiment and the one analysing memory B-cell responses, the Omicron-specific vaccine showed no significant advantage over the original.

The reason one feels ambivalent reading that is that, logically, it would seem that it should be possible to produce a new vaccine that produces gangbusters immunity from Omicron, right? The vaccines train the body to recognize the spike protein on the coronavirus; the reason Omicron is able to evade immunity in so many is because its heavily mutated spike looks so different from that of the original Wuhan virus. Our antibodies, which have been tailored to spot that Wuhan strain, don’t “recognize” it. The obvious solution: Develop a new vaccine that’s keyed to the distinct spike protein of Omicron instead of the original virus. That’ll cause our bodies to develop antibodies that do recognize the new variant and attack it more efficiently.

So how come it didn’t work that way in the macaques?

The answer may have to do with something called “original antigenic sin,” a concept scientists have been warning about since Omicron first erupted in November. Yes, they conceded, Pfizer and Moderna could easily whip up a new vaccine tailored to the new variant, but that doesn’t guarantee that it would perform better against Omicron than the current version. That’s because the body’s first look at a particular virus “imprints” certain information about that virus on its immune system and that imprinting may dictate how the immune system responds forever even as the virus changes. If your first look at the coronavirus was the spike protein on the Wuhan strain via vaccination and then later you’re exposed to the spike protein on Omicron via a booster, your body may continue to react to the spike on the Wuhan strain due to the initial “imprinting.” Derek Lowe explains:

A person’s first exposure to a type of virus, for example, can have a noticeable effect on their later responses to similar ones. This is most easily demonstrated with flu viruses, which notoriously change from year to year within a couple of broad families (influenza A and B). The first flu you get as a child or infant can set you up for your ability to respond to various later varieties, but it should be noted that this can be either a less robust or a more robust response later on. Similarly, there’s some evidence of immunological imprinting having an effect in the current pandemic based on responses to earlier types of coronavirus infection. That’s one reason I don’t like the “original sin” phrasing, because it makes things sound like the consequences are always some sort of irreparable wound. In reality, it can go either way. The exact mechanisms behind this effect aren’t completely worked out – you can easily see how memory B and T cells could respond more quickly to a close-but-not-quite later infection, but there’s clearly more to it than that.

I assume that the more different a variant is from the original strain, the more likely it is that a new vaccine tailored to that variant would outperform a vaccine based on the original strain. Evidently, for all its mutations, Omicron just isn’t different enough from the Wuhan virus to overcome the problem of “original antigenic sin.”

Which, again, isn’t necessarily a bad thing. What it means is that the original vaccines continue to work well even against strains as wild and woolly as Omicron. Pretty efficient.

Should unvaccinated people continue to get those original vaccines, though? If you have no immunity to COVID via vaccination or infection, you could get the Omicron-specific vaccine and “imprint” the spike protein of that strain onto your immune system instead. That might leave you better situated than those of us who got the original vaccine to fend off future variants. Scientists are wary of that idea, though, for a simple reason: What if the next variant that arises is a substrain of Delta rather than Omicron? How would the people “imprinted” with Omicron immunity cope with that?

Maybe not well. “[D]ata have begun to emerge that suggest that an Omicron-based vaccine would not be ideal if given on its own, because Omicron may not generate the same level of cross-protection as the original vaccine strain does,” Stat notes. A study of mice supports that theory: “The study also looked at the Omicron-specific vaccine in ‘naive’ mice — those that had not previously been immunized — and found that the rodents produced high levels of potent antibodies against Omicron. But those antibodies had a limited ability to inhibit other key variants of COVID-19.”

The same problem is seen with Omicron and natural immunity. If getting infected with Omicron is your first exposure to COVID, “imprinting” you with information from that variant, you don’t do well against other strains:

Think of it like a tree with branches. If your original exposure to the virus was the spike protein of the Wuhan strain, you were “imprinted” with information about the trunk. Presumably that’s enough to help you recognize any branch on it, at least partly. If instead your original exposure is to Omicron or its spike protein, you’re only seeing one branch, not the entire tree. That may leave you ill-prepared to cope with a variant from a different branch. Bottom line: It looks like we’ll be sticking with the original vaccine instead of one specific to Omicron unless the result of the human trials of Omicron’s new booster is very surprising.