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Omicron Poses a Puzzle for Vaccine Makers

As Covid restrictions come down throughout most of the advanced world — even Australia is preparing to welcome international visitors again — public health authorities will need to make decisions on future vaccine protocols. One possibility would be a booster shot formulated specifically for the fast-spreading omicron variant, which is behind the recent growth in infections in the U.S., U.K. and elsewhere. 

Bloomberg Opinion columnist Therese Raphael and Bloomberg Intelligence pharmaceutical analyst Sam Fazeli discuss a new study that casts doubt on whether such a variant-specific vaccine is worth it.

Therese Raphael: You previously said that an omicron-specific vaccine might make sense, given the ultra-high transmissibility of the variant and also the high rate of reinfections. But you stressed that the jury was still out because of a lack of data. Now we have the results of an animal study that measured the impact of Moderna’s mRNA booster against the omicron variant. What did we learn?

Sam Fazeli:  Several things. The omicron-specific shot did not induce more or better antibodies against omicron than Moderna’s current Spikevax vaccine. Not only was there not much difference in neutralizing antibodies, PCR tests show that both shots, given as boosters, were able to protect animal lungs against severe pathology and rapidly clear the virus. T-cells, the body’s other arm of the immune response, were also impacted in the same way with both types of shot.

A similar thing was also seen with a vaccine Moderna developed and tested in humans for the beta variant (which circulated in some countries late in 2020). That shot increased neutralization against the beta variant 35 times when used as a booster, only slightly higher than the 32 times when its regular Spikevax shot was used. 

If a similar finding is confirmed by the human trials of the omicron vaccine, it means the vaccines we have will probably work just as well as ones developed to target specific strains, without the need for regular updates.

TR: One argument for a variant-specific shot is that it could include parts of the virus that have undergone substantial changes from the delta or alpha variants. Does this new data suggest there aren’t any real advantages to that?

SF: Based on this animal study, yes, that’s exactly what the data suggest. But we need to see what happens in people, where the response may be different. The lack of a stronger response could be due to the immune system responding to repeated infections or vaccinations by increasing antibody production against the first antigen it experienced. Or it could be because the antibody-making memory B-cells have developed the ability to recognize any variant once a third shot or an infection stimulates them again. This still needs to be worked out and if found to be the case, that would back the idea of not needing variant specific shots.

TR: Could the omicron vaccine provide a longer immune response even if it’s not substantially different?

SF: It could, but we need time to see whether the immune response to having a booster with the current vaccine is any different to that after an omicron-specific shot.

TR: If there are no advantages of an omicron shot, do we know that it is at least not inferior to existing shots. For example, do we know if the immunity provided by an omicron shot works against delta and other variants and whether it would work as well in those who are unvaccinated?

SF: Good question. I have seen data using a novel mRNA technology which has not been tested in humans that showed that mice, which were previously immunized, failed to show increased neutralizing antibody levels against omicron following an omicron-targeted boost. And there is another mouse study that showed the vaccine was effective against omicron but not other variants. This just goes to show how complicated it can be to determine the best vaccine option.

TR: Maybe we should skip the omicron vaccine and put all our future vaccine eggs in the “polyvalent” basket — in a vaccine that can be effective against different variants? Also, if we don’t really need an omicron specific vaccine, does that change calculations on who might need a fourth shot and when?

SF: We’ll need to get the confirmation from the human trials, possibly next month, to confirm the animal study results. If an omicron-specific shot isn’t better than the current vaccine, we would need to assess how the vaccine effectiveness from a third shot wanes balanced against the relatively lower risk of hospitalization with omicron, to decide who should receive a fourth shot, and when.

But a polyvalent vaccine would be a good idea in any case — if we can actually develop one and test it. That’s the difficult part. To develop a new vaccine it would need to be tested all over again in a large study comparing it to current vaccines. And given the level of immunity in the population, either from prior vaccination or infection, it will need to be a very large study over a relatively long period of time to be able to tease out an efficacy difference.

Look at how long it is taking Sanofi and GlaxoSmithKline to get a readout from their Phase III trial of their vaccine candidate. It will be even harder to show a difference in hospitalization rates given the likely broad use of antiviral drugs.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Therese Raphael is a columnist for Bloomberg Opinion. She was editorial page editor of the Wall Street Journal Europe.

Sam Fazeli is senior pharmaceuticals analyst for Bloomberg Intelligence and director of research for EMEA.

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