Should we get an Omicron-specific vaccine?

Who to vaccinate further and with what kind of jab are two major decisions facing public health authorities this year. Bloomberg Opinion columnist Therese Raphael and Bloomberg Intelligence senior pharmaceutical analyst Sam Fazeli discuss why an omicron vaccine might be desirable, provided certain conditions are met. 

Therese Raphael: We are now getting more data — including in the U.K. REACT study — that suggests not only does the omicron variant spread faster, but that there are also more reinfections with omicron. What explains those higher levels of reinfection?

Sam Fazeli:  It’s all to do with this variant’s ability to bypass antibody protection in vaccinated individuals, especially those with just two doses. Data from the U.K. Health Security Agency has shown that just a few months after the second dose, the level of protection against infection with omicron is no more than about 10%. This happens because the virus has amassed so many changes in its spike protein that lower levels of antibodies cannot stop it from infecting cells. While some of this protection is restored after a third shot of the same vaccine, it is still only at about 50% at 10 or more weeks after the shot compared with 90% versus a delta infection.

It’s important to note, however, that all we are talking about here is protection against an infection. Vaccinated people, particularly those with three doses, have a very high level of protection against severe disease requiring hospitalization.

Therese Raphael: Do the number of breakthrough infections suggest that an omicron-specific shot now makes sense?

Sam Fazeli: As I noted, protection against hospitalization after an omicron infection still remains high, though there are some signs of decline over time. But it may be desirable to vaccinate people with an omicron-specific shot if it provides a broader immunity that includes the parts of the virus that have undergone substantial change versus the delta or alpha variants. This idea is supported by the finding that an omicron infection in vaccinated individuals can activate antibody producing B-cells that better target omicron. Whether the same happens with T-cells, which are thought to provide longer-lasting immunity, is not yet known.

Therese Raphael: Pfizer-BioNTech has begun a trial on 1,420 subjects to test omicron-specific shots. Is it really necessary to have a variant-specific shot though, given that we are seeing such low levels of severe disease with omicron? Would this be mainly for older or more vulnerable populations?

Sam Fazeli: That’s a great question and one that the vaccine companies need to answer. With Pfizer-BioNTech and Moderna having already started their trials, they need to answer several critical questions. 

First, is a third or fourth omicron shot better than a standard shot when it comes to the omicron variant? Second, how does that immunity work against delta and other variants, which is important as they have not been eradicated? And third, we need to understand how two omicron shots would work in unvaccinated people. Do these shots broaden the immune reaction, both for antibodies and T-cells? How do they affect immune memory and longevity of immune response?

Therese Raphael: There is already work on developing a so-called “polyvalent” vaccine that targets different parts of the virus and would be effective against different variants. Is there a case for just holding out for a vaccine that has those broad powers?

Sam Fazeli: A polyvalent vaccine can, in theory, provide broader, longer-lasting immunity than existing vaccines, but that has yet to be tested. While neutralizing antibodies most often target the spike protein, there are antibodies to other antigens on the surface of the virus — which would be targeted by a polyvalent vaccine — that can help eliminate the virus through other processes. There is also the likelihood that broader T-cell reactivity will help manage disease severity further. 

But the issue is determining who should receive such a vaccine and whether it indeed provides that added benefit. To reduce the risk of hospitalization by 95%, instead of the current 89% risk reduction against omicron 10 weeks or more after a third shot, would require a massive trial, especially as we will soon have relatively broad access to antiviral drugs. So a lot of thought needs to go into this. England’s Chief Medical Officer Chris Whitty has also said such vaccines are probably five years away. If so, we’ll need to make decisions about the vaccines we have for now. 

Therese Raphael: Finally, are there supply constraints and distribution issues to consider here? And given what we now know about omicron, what’s your thinking about whether and when the majority of people would need a fourth shot?

Sam Fazeli: It all depends on the trial results. If the trial shows that third or fourth shots of an omicron-specific vaccine improve the depth and breadth of the immune response versus vaccination with the current vaccine, then some billion or so doses in 2022 may be required for boosters in high income countries. This still leaves many billions available for low- to middle-income countries.

As regards the timing of omicron boosters, it may be best to save this for next autumn. Many people have already been infected with omicron, though we don’t know how good the immune reaction to the infection is. We also don’t know how long protection lasts. But what governments do will be driven by the desire to keep their economies open, which may mean fourth shots starting as early as April or May, at least for older and more vulnerable segments of the population. Israel has already done this and is now recommending (though not mandating) them for anyone over 18.