In recent days, a number of studies that attempt to measure the efficacy of covid-19 vaccines against the omicron variant have been published. The number of these studies is very limited and, above all, the number of patients studied is very limited. This can be considered their first weakness.

What can be measured at the present time is the capacity of the antibodies generated by the vaccines, by the booster dose given to individuals who were infected and by the third dose given to vulnerable persons.

A priori, each of the mutations in the spicule protein has a possible action that has an impact on the capacity for infection, and not only on the binding of neutralizing antibodies. The process is much more complicated because the whole set of these mutations and their possible interactions, hitherto unknown, must be taken into account.

The studies that are appearing at the moment measure whether the antibody titer decreases or not against the new variant, but the effectiveness of the vaccine cannot be evaluated with this data alone. The system for measuring these variations in antibody titers is not linear. A 40-fold difference, for example, does not mean that there is a 40-fold reduction compared to other variants.

Finally, the use of different technologies can affect the results. The value of the neutralizing antibody titers generated against the infectious omicron virus is not the same as those generated against a pseudovirus; we cannot evaluate in the same way the values shown in the different articles that are appearing because the numbers can mean very different concepts: biological activity, viral escape, etc. Obviously we cannot evaluate the effectiveness of the vaccines and draw conclusions about how well, or how poorly, they will work in real conditions.

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Preliminary data published to date suggest a greater antigenic impact of the omicron variant compared to other variants of concern that have been selected as a result of the evolution of the virus (beta, delta).

There is some discrepancy, to some extent understandable, as to the magnitude of this antigenic impact. It may be due to the different vaccination patterns tested, but also to the methodology used in the different studies.

Both natural isolates and pseudovirus systems have been used which, although to date in previous studies have yielded similar trends, do not always reflect the same degree of neutralization. In addition, neutralizations are performed in different cell lines, some of them specifically modified to increase their susceptibility to SARS-CoV-2 infection.

These cell lines generally overexpress the ACE2 cellular receptor and this can lead to a bias on the degree of neutralization appreciable between variants whose receptor binding regions (RBD) show very disparate properties. Because of the high number of mutations detected in the omicron RBD, it is expected that its ACE2 binding properties are substantially modified compared to other variants. It is important to note that these studies only refer to the impact of omicron on the antibody response induced after infection or vaccination.

Based on omicron sequence analysis, the T-cell response should not be so severely compromised. Therefore, it is expected that the vaccines administered will maintain a significant level of efficacy in preventing serious infections, not so much in reducing the level of infections and re-infections.

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These are the first data that have just come out, not peer-reviewed, but published. This is not the case with the Pfizer note, of which I have only seen one figure pointing to the need for a third dose to combat the omicron variant.

All the data point to a lower neutralizing capacity of the antibodies generated both by infection by the Wuhan ancestral variant and by the different types of vaccines tested. Not all situations are tested in all parallel studies, but all of them show a lower neutralizing capacity against omicron from 5 % to 40 % depending on the cases, which would imply a higher infectivity of the variant even in vaccinated and previously infected individuals. Even in vaccinated infected (hybrid immunity), protection also drops somewhat, although less than in vaccinated or infected alone.

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The definitive answer will come from the comparison of the evolution of the infection in vaccinated and unvaccinated patients.

Since the T-cell response will be at least partially conserved, I believe we already know that the vaccines maintain responses against the variant and will surely be sufficient to maintain their objective of avoiding severe disease and significantly reducing hospitalization.

It is to be expected that the omicron variant will have a spectrum of protection similar to the other variants, since this protection is not so much quantitative (it may be less in number of lymphocytes) but qualitative (effect or no effect) explainable by the immunologic memory that will exist.

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The in vitro tests that are under way are only trying to verify the loss of neutralizing capacity of the antibodies generated by the vaccine due to mutations in the neutralizing epitopes of the virus spicule, but the loss of neutralizing capacity (partial, very unlikely to be total) does not indicate that the vaccine has lost effectiveness, because the cellular immunity generated is much broader and covers many more epitopes of the protein, so that the cellular memory will almost certainly remain preserved against the omicron variant.

The only thing that will probably be observed is a greater contagiousness (transmissibility) as our immune system will not be able to neutralize the virus so quickly in the respiratory mucosa after vaccination.

But this fact need not be alarming as long as there is no loss of effectiveness in the first objective of vaccination, which is to avoid serious disease.

The partial loss of neutralizing capacity of the antibodies generated by the vaccine, by itself, I do not think will be a reason to reformulate the original vaccine given the time and cost required. It is much more important to vaccinate the unvaccinated.

In-vitro cellular immunity results will take a few weeks longer because they are much more complex to perform. In any case, it is always necessary to wait for behavioral data in the real world, to monitor the evolution of the new variant, the course of disease in vaccinated and unvaccinated individuals, and to be very attentive to possible vaccine failures in individuals with a complete and immunocompetent regimen. A partial loss of neutralizing capacity of the antibodies generated by the vaccine is to be expected, but cellular immunity against most of the epitopes of the spicule protein will be preserved. This will imply a greater capacity for contagion or even reinfections, which would be mild and would not imply a loss of vaccine effectiveness.

For the time being, it is unlikely that we are facing a scenario in which Omicron is a true escape variant that would require reformulation of the initial vaccine and revaccination of the entire population, something that would take quite a long time.

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