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Corona vaccination: can the second dose be postponed?

Should the vaccination strategy be changed? It is currently being discussed whether the interval between the first and second vaccination dose should be extended for the corona vaccination - from the previous three weeks to up to eight weeks. As a result, more people could initially receive at least an initial immunization despite scarce supplies. But what do experts say about it? Is that medically justifiable and sensible?

The new vaccines against the SARS-CoV-2 coronavirus raise hope that the corona pandemic can soon be stopped. However, this will only happen when a sufficiently high proportion of the population is vaccinated and thus immune. So far, however, vaccination has only started slowly in Germany and elsewhere: Because only the mRNA vaccine from BioNTech / Pfizer has been approved in the EU so far, supplies are scarce. Many vaccination centers are only working at half speed or are still closed.

Why you have to vaccinate twice

Therefore, it is now being discussed whether one should change the vaccination strategy. The official vaccination protocols for the two mRNA vaccines from BioNTech and Moderna stipulate that each person willing to vaccinate should be given two doses 21 and 28 days apart. These intervals were tested in the clinical studies of both manufacturers. After this, the protective effect of the vaccines sets in at the earliest 14 days after the first vaccination dose, but is only fully developed around a week after the second dose.

The reason for the double vaccination: "Antibodies and T-cell responses that are formed after the second vaccination generally protect better and last longer," explains the German Society for Immunology in a statement. Above all, the T cells formed after the “booster dose” are crucial for immunological memory and ensure that the body recognizes the coronavirus even after a long time.

How well does the first dose protect?

In view of the currently rather sparse supply of vaccines, discussions are now taking place in Great Britain, but also in Germany, as to whether the time of the second vaccination could not be delayed a little. This would have the advantage that more members of the risk groups could then receive an initial immunization from the first few stocks. You would then have at least short-term protection against severe courses of Covid-19.

An argument for such a postponement: Even after the first vaccination dose, the vaccinated people build up immunity to the coronavirus, as the clinical studies by Moderna and BioNTech / Pfizer suggest. According to these, the protective effect of the first vaccination against Covid-19 should have been more than 80 percent shortly before the second dose was administered. However, these data were only collected from a few test subjects.

Does a postponement endanger vaccination success?

"In my opinion, accepting a possibly longer interval until the second vaccination is harmless, at least for the mRNA vaccines, since the vaccinations in the studies showed a very high level of protection against Covid-19 just ten days after the first injection," explains the Infection immunologist Leif-Erik Sander from Charité - Universitätsmedizin Berlin.

However, such a postponement raises the question of whether the vaccination is still sufficiently effective overall. In addition, the immunologists at DGfI explain that a slightly longer time interval may even be more effective. Although no study data for a longer time window are available for the mRNA vaccines, experience with other vaccines suggests that a postponement of a few weeks does not jeopardize the success of the vaccination.

"The interval of 21 days between the first and second vaccination has been shown in other vaccination studies to be the earliest point in time for the second vaccination, because otherwise the first immune reaction blocks the second immune reaction," explains the DGfI. If the second vaccination is given later than 21 days after the first, the second immune reaction could even be more fulminant. However, the experts think it makes sense not to let the interval be longer than 60 days.

Increased risk of developing resistance

Critics of a postponement, however, point to another possible danger: If the first vaccination only offers incomplete vaccination protection, this can lead to the creation of new virus mutants against which the vaccines no longer work. This becomes possible, for example, if a partially immunized patient becomes infected with SARS-CoV-2 and the virus can persist in him for longer despite the initial vaccination.

This case could especially occur in older people because their immune response is weaker than in younger people anyway, as virologist Alexander Kekulé explains. The coronavirus would then have a chance of developing so-called escape mutations in these patients - changes to its spike protein that are not contained in the vaccine RNAs. As a result, the immune system then produces antibodies that no longer perfectly match the viral proteins and therefore do not disable it.

According to initial studies, the particularly contagious virus mutant B.1.1.7. in a patient whose immune system was weakened. As a result, the virus was able to go through more cycles of reproduction and thus had more time to mutate. Although there is so far no evidence that this mutation makes the vaccines less effective, this could be the case with newly emerging mutants in incompletely vaccinated persons.

Disagreement among the experts

Due to this scenario and the so far sparse data on the protective effect of only one vaccination dose, some virologists and immunologists advise against postponing the second corona vaccination. In Kekulé's view, the normal interval between doses should be maintained at least for those over 75 years of age in order to be safe with these high-risk patients. However, the virologist may consider it justifiable to widen the interval when vaccinating the general population

Other experts, on the other hand, see a postponement of the second vaccination for up to 60 days in view of the continuing rampant infections - also in the risk groups. "This means that vaccination doses that are now available should not be withheld for a second vaccination, but should be used for a primary immunization of as many people in the risk groups as possible," said the immunologists at DGfI.

However, they recommend carrying out accompanying scientific studies on the effects of extending the vaccination intervals up to 60 days. Among other things, the amount of neutralizing antibodies formed, in particular the so-called neutralizing secretory immunoglobulin A, should be measured. Subjects could be volunteers from medical and nursing staff who themselves do not belong to vulnerable groups.

Then it becomes logistically more complicated

Even in the event of a postponement, however, it would have to be ensured that all vaccinated persons received their second dose in good time. "This represents an additional challenge when planning the second vaccination, which must ultimately be carried out," says the virologist Thomas Mertens from the Ulm University Hospital.

It is not yet clear whether there will be such an extension of the vaccination interval in Germany at all. The approval of other vaccines such as Moderna's mRNA vaccine and AstraZeneca's carrier virus-based vaccine may also mean that this measure will not be necessary. The Moderna vaccine was approved by the EU yesterday, the AstraZeneca vaccine is already being vaccinated in Great Britain, among others.

Source: German Society for Immunology, Robert Koch Institute, Science Media Center

 

January 7, 2021

- Nadja Podbregar