I was watching Vox’s video, Big questions about the Covid booster shot, answered, which references the New York Times article Omicron Prompts Swift Reconsideration of Boosters Among Scientists.

In these sources, it is mentioned that the scientific community used to be mostly against giving a COVID booster shot to the less vulnerable. With the emergence of the Omicron variant, the same scientists who were opposed to booster shots had changed their minds.

However, no complete explanation was given for this in these sources, and my further research led to nothing concrete.

As per my understanding, vaccinations provide protection both by increasing antibodies in the blood (which provides protection for about 2 weeks), or by increasing B cells which would be able to identify the spike protein of the virus and help create antibodies (which provides more long-term protection).

With the SARS-CoV-2 Omicron variant, my understanding is that there were several mutations in the spike protein, which means that B cells may not recognize it or the antibodies might not bind to its receptors. If this is the concern, then how was the Omicron variant a reason for extra doses of the preexisting vaccines?

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    $\begingroup$ I think it's important to recognize that scientists "against giving a booster shot to the less vulnerable" had that position for public health reasons of reserving the available doses for those who had not yet received any vaccine. $\endgroup$
    – Bryan Krause
    Commented Dec 9, 2021 at 15:31
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    $\begingroup$ Just because Omicron has come out, it doesn't mean the others have died down. They are still about. Some vaccines may not be effective against omicron but they may be effective against all the others before or even after omicron. Note that vaccines are not the magic bullet that some govts and newspapers sell it to be - you can still get infected after having the vaccine. There is no magic bullet. $\endgroup$
    – cup
    Commented Dec 10, 2021 at 8:41
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    $\begingroup$ This came out today (BBC): "Two doses of a Covid vaccine are not enough to stop you catching the Omicron variant, UK scientists have warned. Early analysis of UK Omicron and Delta cases showed the vaccines were less effective at stopping the new variant. However, a third booster dose significantly increased protection to around 75%." $\endgroup$
    – David K
    Commented Dec 10, 2021 at 17:16
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    $\begingroup$ @BryanKrause The scientists against giving the booster shot to the less vulnerable are motivated by the risks to individuals. "One big reason for the panel’s skepticism: the risk of myocarditis and pericarditis … particularly in men aged 18 to 25. Those patients, several panelists said, are also at the lowest risk of Covid." statnews.com/2021/10/14/… $\endgroup$
    – endolith
    Commented Feb 5, 2022 at 23:24

5 Answers 5


(note: I'm simplifying things a bit here by only talking about antibodies; I don't mean to downplay other aspects of the immune response, just to keep it focused for a lay audience)

Natural antibody responses by the immune system are polyclonal - there isn't just one antibody to meet one antigen, but numerous different antibodies that may each recognize a slightly different part of the antigen.

Antibody binding (or ligand binding more generally) is also not "all-or-none". We usually describe ligand binding in biology by "affinity". When a receptor has a lower affinity for some ligand, you need higher concentrations of the ligand to saturate the same fraction of receptors (or vice-versa).

You can expect that antibodies raised against a coronavirus spike protein may have lower affinity for spike proteins altered by mutations in a viral lineage. It's also reasonable to expect that the more changes (mutations) there are, the more the affinity will change and the more antibody clones will be affected.

It's still unlikely that every different antibody in a polyclonal response will stop binding completely, but the reduced affinity is likely to equate to a reduced immunity. It's not easy to quantify this at the level of the whole organism, but it's normal to do in vitro binding experiments where you mix a mutated viral protein with some antibodies raised to a previous version. The extent of binding is a good qualitative approximation for how well immune responses will transfer.

Probably the best approach would be to give boosters with a spike closer to the new dominant variant at any point. However, that requires testing and manufacturing and simply isn't going to happen in time to be useful. In the meantime, the best alternative is to be prepared against the next-closest thing. As an approximation, you might say that if binding affinities are reduced by 50%, then if you can double your antibody response you've got about the same immunity.

Previous experience with the delta variant showed that antibodies raised in response to vaccination with the original spike protein still bound, even if they didn't bind as strongly. It seems like vaccinated people had good protection against delta even if it wasn't as good as their protection against the original strains. We can expect the same trend for the new variant, though we'll need further data to understand quantitatively where that protection level is at.

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    $\begingroup$ We're getting the first, non-peer reviewed yet, reports and it doesn't look good: medrxiv.org/content/10.1101/2021.12.07.21267432v2.full.pdf. I need to go through it a bit more carefully, but they are claiming that two jabs of BionTech gives 0% protection from omicron. Apparently, the best results are a combination of vaccine and infection. This is only about omicron and only about several months past the first vaccine, it shouldn't be taken as an indication of the efficacy of recent vaccination. $\endgroup$
    – terdon
    Commented Dec 10, 2021 at 18:24
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    $\begingroup$ @terdon 0% protection against what? Infection / transmission / symptomatic cases / hospitalisation / death / all of the above? $\endgroup$
    – Tim
    Commented Dec 11, 2021 at 16:10
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    $\begingroup$ @Tim none of the above. This is an in vitro study using blood serum extracted from people with different combinations of vaccine doses. The serum should contain antibodies against the virus, which should be able to neutralize the virus when put in a solution with it. The paper claims that serum from individuals with only 2 vaccination doses (no booster) had no effect on Omicron (but did on Delta). Exactly what such an in vitro study means for the effects in vivo is unclear, but it isn't encouraging. The good news is that sera from people who had had a booster shot did better. $\endgroup$
    – terdon
    Commented Dec 11, 2021 at 16:29
  • $\begingroup$ @terdon Interesting. I would have thought a spike that mutated past antibodies completely would also not bind to the same receptor. But I guess that's too much to hope for. $\endgroup$
    – Seth
    Commented Dec 12, 2021 at 23:13
  • $\begingroup$ "...not "all-or-none". (...) When a receptor has a lower affinity for some ligand, you need higher concentrations..." - Would like to know about role of concentration in respect of antibodies compared to t-cells and their receptors. $\endgroup$ Commented Dec 14, 2021 at 7:51

Some Clarification:

What changed the mind of expert? Even if Omicron is not more dangerous than delta. (dangerous here: For 1000 persons, How many needs hospitalization, ICU, will got sequels and long covid or will die?)

Omicron is "at least time 2" more contagious. In terms of spreading capability, it is a monster. It is estimated that case double each 3 days (All number you are seeing right now will evolve as we get more data).

EDIT: This number is changing as new data emerge, cdc only state that omicron is more transmissible: cdc. The number I gave 2 times more transmissible and doubling every 3 days are from non peer reviewed source, take them with a grain of salt. Other sources are more dramatic, to have the real number science need a bit more time and more data.

Omicron seems to be able to reinfect people infected previously.

All together, those two points are scary. We expect to have a lot of covid case in a shorter time span. Followed by hospitalization with all the negative attached to it. To a degree we have never seen. Yes you heard it right, we expect it to be bad... Hospital saturation, economic going slow.

In this context, a booster shot may impose itself as a way to preserve life and avoid hospital saturation. Early data show a weak protection to infection from previous infection or vaccination (but everything help in this regard)Omicron likely to weaken COVID vaccine protection. But we still hope that the third shoot preserve from dangerous form of the disease.

Summary : The Goal of a third shot is to avoid a saturation of the health care system, a lot of people still seem to minimize this eventuality, but it is terrible. It is what cause government to impose shutdown and lockdown.


(Update Dec 15: See update in my 2nd answer below, describing new study based on actual patient data, published in just the last few days, relevant to the current question.)

This answer is a supplement to the answer of @Bryan Krause. It responds to a comment by original questioner @hb20007, who pointed out that

"My question was about the seeming logical contradiction where the concern with the Omicron variant is that it might have too many mutations in the spike protein to be recognizable by existing immune cells, but the proposed solution is extra doses of the same old vaccines."

This comment makes a reasonable point: there might indeed be a 'logical contradiction' if it were true that a booster only provides more of the very same immune response that the previous dose(s) evoked.

But in fact, vaccine doses of identical content not only can generally produce different immune responses in different people: it's also the case that successive doses of the same vaccine can also produce different immune responses in one and the same vaccinated person. This is fundamentally due to the presence, as part of the normal mechanism of immune response, of a stage that involves random mutations, even hypermutation (followed by selection) of the somatic genes encoding antibody proteins.

When a booster vaccine is given, it not only boosts the quantity of the immune response, it also causes a process called antibody affinity maturation. (See also a recent review in 'Frontiers in Immunology'.) The mutations involved in this process can increase the diversity of the immune response. This mutation round is built-in to the system, so this is 'good' mutation (when it goes to plan*) -- and it is followed by selection of those mutation products that have affinity for the antigen.

As a result, the enhanced immune response after a booster vaccine is not just a 'carbon copy' of the earlier immune response. As long as the antigen underlying the vaccine retains some relevant cross-reactivity with a variant antigen of concern, there is the possibility of increasing the response against the variant antigen by the booster.

At the same time, it does seem obviously more desirable that the vaccine against a variant antigen should be tailored as closely as possible to any new antigenic identity of concern. The chances of relevant protection are so much the better, as the resemblance between the vaccine antigen and the variant antigen is closer. So far, the experts who have made recent statements, about the value of boosters using the original coronavirus vaccines types, do not seem to be denying (as far as I read them) that a variant vaccine tailored to the mutated variant antigen would be desirable, but they are emphasising the point that the potential utility of the current vaccines is still there in spite of the mutations.

Perhaps a variant coronavirus vaccine will be produced along lines parallel to the annual flu vaccines, where an existing manufacturing and formulation method is repeated for the variant except for the identity of the antigen(s) included. Because of the commonality these are subjected to (abbreviated) testing and regulatory examination. There may be more happening in the reserach pipelines for the coronavirus than we are currently getting news of -- but we are not there yet, and the only vaccines around appear to be those targeted on a spike protein with sequence close to that of the original SARS-Cov-2.

*(Somatic hypermutation does occasionally suffer genetic accidents, see for example (https://pubmed.ncbi.nlm.nih.gov/30874354/). But it remains a vital stage in the normal immune response.)

  • $\begingroup$ "...there is the possibility of increasing the response against the variant antigen..." Could you please add some reference? That's because there was no specifity "at all" before? Possibility in a literal sense? $\endgroup$ Commented Dec 14, 2021 at 8:00
  • $\begingroup$ @Peter Bernhard -- I didn't say or suggest there was 'no specificity at all before'. Also, according to my understanding, the reports of reduced effect of the immune response arising from the current vaccines against the new variant are just that, reduced effect, they do not say that there is no binding effect at all. The references I've given about the hypermutation and affinity maturation already appear to provide what you asked. $\endgroup$
    – terry-s
    Commented Dec 14, 2021 at 12:11
  • $\begingroup$ @hb20007 -- thank you! $\endgroup$
    – terry-s
    Commented Dec 14, 2021 at 12:12
  • $\begingroup$ No pun intended (globally) drawing your attention to your source "Frontiers...", citing: "Indeed, the periphery may offer more suitable sites for optimization because these regions are typically more flexible and tolerant to mutations than central sites." The more affinity maturation the more cross-reactivity (which is more)? Thanks! $\endgroup$ Commented Dec 16, 2021 at 11:42

Pathogens (and unfortunately sometimes unrelated things) have antigenic sites. These antigenic sites are responsible for acting as antigens by which an antibody can respond to, or perhaps a larger immune response can initiate. Viruses and pathogens are constantly evolving to try to better hide from their hosts' immune systems, called the Red Queen hypothesis.

One reason why the Omicron variant may be more transmissible than the current Delta variant is because of difference in these antigenic sites. If an immune cell can't recognize a pathogen, the pathogen can sneak by undetected and may later initiate infection. In essence, subtle differences in new variants are what give those variants a potential advantage over each other. This variation is a source of evolution, and you can't forget that viruses are evolving too, just like every other species on Earth. Often, viruses are phylogenetically monitored for their level of divergence to try to plan ahead and determine which viruses are going to be the most troublesome next year.

So, what needs to be investigated now? Well, much research is being done trying to figure out how much conserved information there is between variants, called homology, as well as other factors like hospitalization, virulence, and so on. Depending on how alike Omicron is to Delta will depend on how well our vaccines are against it. If our vaccines have a chance at doing something, then being immunized right now is absolutely crucial in preventing the evolution of future variants and later strains that may be more pathogenic. While it may seem like a time to rest on our laurels, the Omicron variant gives rise to new genetic variation that may result in future evolution and extend this pandemic long beyond what we have the patience for. It is our responsibility to beat out that evolution before it can occur.

But, then again, the immune system is a complicated mess of unintuitive situations, and I would encourage you to read into all of the science a little further.

Here are some resources:

A little bit about the immune system.

About how viruses must balance transmission and virulence (lethality).

How evolution helps us understand viruses.

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    $\begingroup$ Be careful: The transmission rate has nothing to do with the immune system. This is a "simple" stick and fit to the receptor which is needed for cell entry. That this is the same as we are vaccinating against has reasons. $\endgroup$
    – Chris
    Commented Dec 9, 2021 at 16:06
  • $\begingroup$ I'm not talking about the lock and key model, I'm discussing the evolution of a virus. Viruses with high transmission are weakly selected against in virulence, they can kill people because they spread easily. Viruses with low transmission can't get away with this, and so virulence is selected against. Variants with differences in antigenic sites can become more transmissible. Why? Because the immune system is naïve to them. $\endgroup$
    – BrownBag
    Commented Dec 9, 2021 at 16:27
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    $\begingroup$ This answer has a lot of great information but I feel like it does not completely answer my question. My question was about the seeming logical contradiction where the concern with the Omicron variant is that it might have too many mutations in the spike protein to be recognizable by existing immune cells, but the proposed solution is extra doses of the same old vaccines. $\endgroup$
    – hb20007
    Commented Dec 9, 2021 at 16:30
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    $\begingroup$ Hey that's fair. Allow me to clarify. Boosters for everyone were previously recommended against so that people who were at high risk had access to them, because their immune responses are typically weak and the level of immunity they achieve isn't as great as say a young person. But now, we have a new variant to worry about, and there's a reasonable chance that, because of evolutionary homology, our vaccines may do something about it. To prevent this variant from spreading and creating another worse variant, it's important to immunize ourselves as best as possible. $\endgroup$
    – BrownBag
    Commented Dec 9, 2021 at 16:35
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    $\begingroup$ @BrownBag: Can you add the information to the answer, please? Comments may be deleted at any time. (But without "Edit:", "Update:", or similar - the answer should appear as if it was written right now.) $\endgroup$ Commented Dec 10, 2021 at 10:07

This is a second/supplementary answer, bringing newly-published data relevant to the question

"Why are scientists saying that the Omicron COVID-19 variant is a reason to get a booster?" and in particular, why "the proposed solution is extra doses of the same old vaccines" (when initial courses of those original vaccines have shown clear signs of relative ineffectiveness against this new variant).

My earlier answer (Dec 11) tried to describe the part of the normal immune system that enables a booster vaccine dose to generate a diversified immune response, through the intervention of the random-mutation part of the system.

While this describes an in-principle mechanism for booster effectiveness against Omicron in the current scenario, descriptions of mechanism inevitably leave aside an important point : 'how effective' can such booster vaccine doses be?

To answer that, as the old saying goes, "the proof of the pudding is in the eating". But with the Omicron variant so new, the main scientific results until the last few days had to be based on laboratory-bench testing of blood-serum/antibody samples.

Naturally of great interest is actual clinical data, and within the last week, the original laboratory data have been supplemented by publication of a (preprint) report of a UK-based case-control study surveying actual patients.

Again, since the Omicron variant is still so new, and the Omicron-caused diseases still so recent and perhaps in early stages, the new study is "unable to determine protection against severe forms of disease, due to the small number of Omicron cases so far, and the natural lag between infection and more severe outcomes". Nevertheless, the new results do show that the indications from the laboratory antibody studies are being confirmed in the early clinical experiences of covid-19 due to Omicron, i.e. the results are showing that booster dosing with the Pfizer-Biontech vaccine gives a marked improvement in protection against the Omicron-caused disease seen so far compared with the effects of either of the previous 2-dose vaccine programs alone.

The report is still too recent to have been refereed, but can be read at "Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern". The authors come from hospitals and research institutions in London, Oxford and Cambridge plus the national health-security agency. The data analysis was enabled by the UK National Immunisation Management System with details of covid vaccinees.

The authors' introduction cites previous "preliminary neutralisation data" (that is, laboratory studies of antibody inactivation of virus) against the Omicron variant.

"The South African and German studies, as well as unpublished data from the UK, indicate a 20- to 40-fold reduction in neutralising activity in sera from 2-dose [Pfizer/Biontech] vaccine recipients compared to early pandemic viruses, and at least a 10-fold reduction compared to the Delta variant." Thus the "effectiveness [of available vaccines] against symptomatic disease with the Omicron variant is significantly lower than with the Delta variant."

Among those who had received 2 doses of [Pfizer/Biontech], vaccine effectiveness [against Omicron] was 88.0% ... 2-9 weeks after dose 2, dropping to 48.5% ... at 10-14 weeks post dose 2 and dropping further to between 34 and 37% from 15 weeks post dose 2.

Vaccine effectiveness increased to 75.5% ... after the booster among those who had received [Pfizer/Biontech] as the primary course."

"Among those who had received 2 doses of [Oxford/AstraZeneca], there was no protective effect of vaccination against symptomatic disease with Omicron from 15 weeks after the second dose.

Among those who received [Oxford/AstraZeneca] as the primary course, from 2 weeks after a [Pfizer/Biontech] booster dose, vaccine effectiveness [against Omicron] increased to 71.4% ... .

"All of the Omicron estimates are subject to significant uncertainty with wide confidence intervals", because of the low number of patients with identified Omicron-caused disease (just under 600 patients between 27 November when Omicron patients began to be identifiable and 9 December when the data were obtained, although Delta patients and test-negative controls in the data came from a larger time-interval and numbered over 56,000 and over 130,000 respectively.

Thus the new study concludes that

"a booster dose of [Pfizer/Biontech] following either [Oxford/AstraZeneca] or [Pfizer/Biontech] as a primary course" brings "moderate to high vaccine effectiveness against mild infection [due to Omicron] of 70-75% ... in the early period after [the booster dose]."

By contrast, for patients without booster doses,

"Our findings indicate that 2 doses of vaccination with [Pfizer/Biontech,] or [Oxford/AstraZeneca] are insufficient to give adequate levels of protection against infection and mild disease with the Omicron variant, although we cannot comment on protection against severe disease."

"Booster doses of [Pfizer/Biontech] provide a significant increase in protection against mild disease and are likely to offer even greater levels of protection against severe disease. As such our findings support maximising coverage with third doses of vaccine in highly vaccinated populations such as the UK. Further follow-up will be needed to assess the duration of protection of booster vaccination."

So the boosted patients in the study experienced very much better protection against Omicron than patients who had only received two doses, whether of Oxford/AstraZeneca or Pfizer/Biontech.

In the US, in reaction to recent results, "Dr. Anthony S. Fauci said Wednesday [Dec 15] ... that “at this point, there is no need for a very specific booster” designed especially to fight Omicron." New York Times.


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