Third dose of vaccine: searching for evidence

This article was published on
August 16, 2021

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So far, there are no published data to support the need for a third dose for everyone. Some studies suggest that it could benefit people with transplants, although there is much stronger evidence that vaccines also protect this population.

So far, there are no published data to support the need for a third dose for everyone. Some studies suggest that it could benefit people with transplants, although there is much stronger evidence that vaccines also protect this population.


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By Marcos López Hoyos, president of the Spanish Society of Immunoloy (SEI) and ex-secratary of the Spanish Society of Transplantation (SET).

With the number of vaccinated people in Spain barely reaching 20%, a worldwide debate was opened about the need for a thirddose of the covid-19 vaccine in the population with the full regimen. Regardless of the commercial interests of the spokespersons who introduced it, the question may be of scientific interest.

In theory, such a debate is based on the loss of antibodies that the manufacturers of the vaccines, especially the Pfizer company, seem to have encountered. However, the data have not yet been published in any scientific journal.

So far we know the published duration of circulating antibodies in blood from Comirnaty - up to 90 days; from Spikevax -just over 200 days; and from Janssen - eight months for antibodies and specificCD4 T-cells for protein S. Interestingly, the importance of the antibodies alone is given, but no data are shown or discussed on the persistence of B andT memory cells – Janssen’s does have them.

These are precisely the populations that, together with long-lived plasma cells, vaccination is intended to induce so that our immune system responds quickly and in a specialised manner in the event of a new encounter with the virus.

In transplant recipients

Antibodies protect, but we need to have a well-established complete cellular and memory response. In natural infection-generated immunity - a high-risk procedure to achieve immunity - we know from rigorous literature that all these components are in place until almost a year after infection. It stands to reason that something similar oreven better would happen with vaccines.

However, there is one situation where the third dose is thought to play its role: that of the immunocompromised population. Immunosuppression is a very broad term that ranges from the elderly -immunosenescence - to patients with primary immunodeficiencies and those immuno suppressed by the underlying disease or by treatment. Of these, it is in transplant recipients that the first evidence supporting the third dose appears to have emerged.

It has been shown in solid organ transplant recipients that the antibody response with messenger RNA vaccines falls to 30-40%,while in the general population it is 90%. One paper has just shown lower antibody production even with the single-dose vaccine, but in a small series of patients, which makes it difficult to assess.


Cell-mediated immunity data are lacking

Again, there is still no consistent data oncell-mediated immunity (T and B), although evidence is beginning to emerge with mixed results.  This lower production of antibodies is associated above all with a time closer to the time of transplantation - when immunosuppression is greater -; with older age - as in the general population -and with the type of transplant - lung, heart, and kidney,rather than liver.

These data are still very preliminary and need to be confirmed in large, multicentre series. As a consequence of this lower effect on antibodies, studies have been proposed to assess the effect of the third dose in transplant recipients who do not produce antibodies after vaccination.

For the time being, several single-centre studies have shown that the third dose is able to induce antibody production in 30-50% of seronegative patients after the second dose.


No detectable antibodies, but with immunity

 This effect of the third dose must beattributed to the fact that, despite no detectable antibodies after the second dose, memory T and B cells had been produced, and re-exposure induces them. The same could be true if these patients had been exposed to the virus.

In fact, the work published so far shows a very low incidence of COVID-19 infection in vaccinated transplant recipients with a complete regimen. In other words, the vaccine protects against infection and, above all, against symptomatic disease. This is the good news and shouldreassure transplant recipients: real-life data show that the vaccine also works in transplant recipients.

Ultimately, scientists are becoming concerned about situations where the vaccine might fail and are investigating them. As always, we need more data and studies to accurately define the situation in transplant recipients. As always, science must be allowed to work.

So far science has proved its worth in thispandemic. Let us give it the resources and means - the budget. And in the meantime, let us be calm and gather evidence before we act rashly.

This article is also available in Spanish.

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