Covid-19: the inevitable third dose

The administration of a third dose of the vaccine against COVID-19 begins to become general throughout the world. United States already approved long ago and the European Medicines Agency has also done the same. But is it inevitable? What reasons are behind this decision?

Third dose or booster dose?

Although it may seem like a semantic question –that there is something to it– from the immunological point of view, the concepts “third dose & rdquor; and “booster dose & rdquor; They are different.

We administer a third dose to those people in whom the response obtained after inoculation of two doses has not been sufficiently robust. This occurs, for example, in patients with immunodeficiencies (primary or acquired) or in those others who are immunosuppressed for medical reasons, as is the case of the transplant patients, who have to take immunosuppressants for life.

For its part, the booster dose is administered to those people in whom the response obtained after the two initial doses was very powerful, but to which it is necessary to inoculate again to reinforce a response that has been weakened. The two main reasons for this weakening are the passage of time and the appearance of new variants.

How long does the immunity conferred by vaccines last?

It depends on the disease rather than the vaccine itself. Some provide strong immunity for many years, such as the yellow fever vaccine, that protects us efficiently almost for life, or mumps, who does it for at least 27 years.

At the opposite extreme we have other diseases such as whooping cough, in which immunity begins to decline 2 to 3 years after immunization.

In an intermediate position would be tetanus, for which it is recommended to administer the full regimen during childhood (5 doses up to 15 years) and subsequently receive a booster dose every 10 years.

So it should come as no surprise that COVID-19 vaccines lose efficacy over time. It happens with all, or with almost all.

How long does the immunity conferred by vaccines against COVID-19 last?

This question does not have, at the moment, a definitive answer, because not enough time has passed. Natural immunity against the four types of coronavirus, similar to SARS-CoV-2, and which cause a third of common colds, is not very long-lasting. That is why we experience these episodes almost every year.

Initial fears about short-lived immunity to SARS-CoV-2 have, fortunately, not been confirmed. Thus, although it is progressively declining, a robust immune response was still observed 8 months after administration of the vaccine. At least before the appearance of the variants.

How do variants influence the efficacy of vaccines?

Much. We must not forget that the immunogen contained in the vaccines we are administering is that of the original virus. And since January 2020 it has rained a lot, and the virus has mutated as well. Thus, each of the variants that have appeared contained progressively more significant differences compared to the original strain, so it was expected that the vaccine efficacy would suffer.

Compared to the variants known until a few weeks ago, it was already observed that the neutralization capacity of the antibodies produced in immunized patients it was quite minor.

The good news was that this lowered immune response was still sufficient to protect the non-vulnerable population effectively, so most of the scientific community did not consider the administration of a general booster dose urgent.

It seemed more urgent to focus efforts on getting as many people as possible vaccinated around the world as soon as possible. Given that we are facing a global disease, not doing so was putting ourselves at risk of the appearance of a new variant that escapes the protection of vaccines. And if that happened, we would go back to the starting box. Enclosures included.

And the omicron variant & mldr;

And the situation changed completely. This variant has caused enormous concern because it is the furthest from the original, since it contains up to 50 mutations with respect to it, an unusually high number. In addition, it has been revealed as extraordinarily infective, much more than all the previous ones.

As if that were not enough, some changes detected had been related to an evasion of the immune system. Therefore, the possibility that omicron escaped vaccines seemed very real.

The preliminary data that we have indicates that neutralizing antibodies against the omicron variant, in people vaccinated with two doses, they are 25 times less than those possessed by these same people compared to the other variants.

The good news is that people who have received three doses reach a level of antibodies against omicron equivalent to that of those immunized with two doses against the rest of the variants.

The inevitable third dose

Or better, as a souvenir. Models predict, and developments in the UK prove it, which omicron will be the predominant variant in Europe in a few weeks. An equivalent situation probably occurs in Latin America, where the variant has already been detected in Brazil, Argentina, Chile and Mexico, although the austral summer may modulate its spread in the short term.

We must, therefore, speed up vaccination in those countries with a low immunization rate and use this booster dose in others to return to the level of immune protection that we had before the appearance of omicron. There doesn’t seem to be any other alternative.

On the other hand, it should be considered reformulating the vaccines to adapt them as soon as possible to the variants that we currently have, something that pharmaceutical companies are able to meet in less than 100 days thanks to new technology and that would obviously make them more effective.

And of course, remember that you have to be vaccinated every year against the flu, so we should not exclude that in the future we will find ourselves in a similar situation with COVID-19.

Covid-19: the inevitable third dose | The conversation