Corona vaccination: can the second dose be postponed??

Extending the interval could free up more vaccine doses for first-time vaccination

So far, the Corona vaccine is in short supply in Germany. Can postponement of second vaccine dose ease bottleneck? © MarianVejcik/ iStock

Should the vaccination strategy be changed? There is currently a debate about whether the interval between the first and second doses of the Corona vaccine should be extended – from the current three weeks to up to eight weeks. This would allow more people to receive at least an initial immunization despite a short supply. But what do expert scientists say? Is this medically justifiable and sensible??

The new SARS-CoV-2 coronavirus vaccines are raising hopes that the corona pandemic may soon be stopped. However, this will only happen when a sufficiently high proportion of the population has been vaccinated and is therefore immune. So far, however, vaccination is off to a slow start in Germany and elsewhere: Because only BioNTech/Pfizer’s mRNA vaccine has been approved in the EU so far, supplies are scarce. Many vaccination centers are only operating at half strength or are still closed.

Covid 19 vaccinations carried out per day in Germany. © Robert Koch Institute

Why vaccination must be given twice

That’s why there is now discussion about whether to change the vaccination strategy. The official vaccination protocols for the two mRNA vaccines from BioNTech and Moderna call for giving each person willing to be vaccinated two doses, 21 and 28 days apart, respectively. These intervals were tested in the clinical trials of both manufacturers. According to them, the protective effect of the vaccines starts at the earliest 14 days after the first vaccine dose, but is not fully developed until about a week after the second dose.

The reason for the double vaccination: "Antibodies and T-cell responses formed after the second vaccination generally protect better and last longer," the German Society for Immunology explains 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 longer period of time.

How well the first dose protects?

In view of the currently still rather sparse supply of vaccine, there is now discussion in Great Britain, among other places, but also in Germany, as to whether the timing of the second vaccination could not be delayed somewhat. This would have the advantage that more members of the risk groups could then receive initial immunization from the first scarce stocks. They would then have at least a short-term protection against severe courses of Covid-19.

One argument for such a shift: even after the first dose of vaccine, vaccinated individuals are already building up immunity to coronavirus, as Moderna and BioNTech/Pfizer clinical trials suggest. According to these, the protective effect of the first vaccination against Covid-19 was more than 80 percent shortly before the second dose was administered. However, these data were only collected from a small number of subjects.

Does postponement jeopardize vaccination success?

"In my view, accepting a possibly prolonged interval until the second vaccination is harmless, at least for the mRNA vaccines, since the vaccinations in the studies showed very high protection against covid-19 already about ten days after the first injection," explains infectious disease immunologist Leif-Erik Sander of Charite – Universitatsmedizin Berlin.

However, such a shift raises questions about whether the vaccination as a whole is then still sufficiently effective. The immunologists of the DGfI explain that a slightly longer time interval may even be more effective under certain circumstances. Although study data on a longer time window are not yet available for the mRNA vaccines, experience with other vaccines suggests that a delay 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 time for the second vaccination, because otherwise the first immune response blocks the second immune response," DGfI explains. If the second vaccination is given later than 21 days after the first, the second immune reaction can be even more fulminant. However, the experts believe it makes sense not to let the interval become longer than 60 days.

Increased risk of resistance

Critics of postponement, however, point to another potential danger: If the first vaccination provides only incomplete protection, this could lead to the emergence of new viral mutants against which the vaccines would then be ineffective. This is possible, for example, when a partially immunized patient becomes infected with SARS-CoV-2 and the virus is able to persist in him or her for a longer period of time despite initial vaccination.

This case could occur especially in older people, because their immune response is weaker than in younger people anyway, as virologist Alexander Kekule, among others, explains. The coronavirus would then have the chance to form 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 produces antibodies that are no longer a perfect match for the viral proteins and therefore do not knock it out.

According to initial studies, the particularly infectious virus mutant B.1.1.7. developed in a patient whose immune system was weakened. Thus, the virus could live through more multiplication cycles and had more time to mutate. Although there is no evidence so far that this mutation makes the vaccines less effective, this could be the case with newly occurring mutants in incompletely vaccinated people.

Disagreement among experts

Among other things, because of this scenario and the so far thin data on the protective effect of only one vaccine dose, some virologists and immunologists advise against postponing the second Corona vaccination. Thus, according to Kekule, the normal interval between doses should be maintained, at least for those over 75 years of age, to be safe in these high-risk patients. However, the virologist believes it may be justifiable to extend the interval when vaccinating the general population

Other experts, on the other hand, consider a postponement of the second vaccination to up to 60 days to be sensible in view of the infections that continue to be rampant – also in the risk groups. "This means that vaccine doses available now should not be withheld for a second vaccination, but should be used for initial immunization of as many people in the risk groups as possible," DGfI immunologists said.

However, they recommend that accompanying scientific studies be conducted on the impact of extending vaccination intervals up to 60 days. Among other things, the amount of neutralizing antibodies produced, especially 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 risk groups.

Logistically, it then becomes more complicated

Even with a postponement, however, it would have to be ensured that all vaccinated persons nevertheless receive their second dose in time. "This presents an additional challenge when planning the second vaccination, which must ultimately take place," virologist Thomas Mertens of the University Hospital in Ulm, Germany, points out.

It is not yet clear whether there will be such an extension of the vaccination interval in Germany at all. It could also be that this measure will not be necessary due to the approval of other vaccines such as Moderna’s mRNA vaccine and AstraZeneca’s carrier virus-based vaccine. The Moderna vaccine was approved by the EU yesterday, and the vaccine from AstraZeneca is already being vaccinated in the UK and elsewhere.

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

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