Studies on boosters: how useful is a fourth vaccination?

The first studies on the effectiveness of the fourth vaccination come from Israel. What speaks for a renewed refresher? Who would it be useful for? And why are some experts reluctant to comment??

The omicron variant dominates the infection process. Adapted vaccines should soon be available, but countries like Israel are already vaccinating with the existing vaccines for the fourth time. Experts have different opinions on who this makes sense for.

Why a fourth vaccination?

The third vaccination significantly increases protection against infection with the omicron variant and also against severe courses. However, this protection also flattens out over time, and the immune response subsides. It is not yet possible to say with certainty how quickly this will happen after the third vaccination. Further booster vaccinations with the existing vaccines should therefore primarily maintain the effectiveness of the vaccination.

This is particularly relevant for older people. According to one, over 80-year-olds need Study by the University of Marburg often at least three vaccinations to form a good immune response. A fourth vaccination could also make sense, since the immune protection probably decreases more quickly. In addition, older people often had their third vaccination several months ago.

A fourth vaccination could also be carried out in the future with a vaccine adapted to the omicron variant. So not only should the effectiveness be maintained, but improved. Because the current vaccines were developed for other virus variants, they no longer work as well against omicron. That could change with an adapted vaccine. BioNTech/Pfizer and Moderna have already started the first clinical studies to investigate an adapted vaccine.

BioNTech and Pfizer want to be able to deliver the first doses by March or April. However, the decision of the European Medicines Agency (EMA) on the approval is not expected until a little later. Germany has ordered another 80 million doses from BioNTech.

Who is already getting a fourth vaccination with the existing vaccines?

At the beginning of January 2022, Israel was the first country to start a broad-based second booster campaign. Since then, over 60-year-olds, medical and nursing staff as well as people with immunodeficiency can be vaccinated a fourth time. More than 600,000 people have now received the fourth dose. For a few days now, a fourth vaccination has also been recommended for people over the age of 18 who belong to a risk group or care for someone at risk.

Some other countries recommend the fourth vaccination for immunocompromised people or other risk groups. In the EU, these are currently Denmark, Sweden and Belgium. Hungary offers a fourth vaccination to anyone who wishes, after medical advice. In Germany, due to a lack of data on effectiveness, the Standing Vaccination Commission has not yet recommended a fourth vaccination, not even for risk groups. Only in exceptional cases is a fourth vaccination given, for example in the case of medical staff in hospitals or in the case of organ transplant recipients.

What do studies say about the effectiveness of the fourth vaccination?

The first data on the effect of the fourth vaccination with the available vaccines come mainly from Israel. Sheba Medical Center conducted two studies in which a total of around 270 people received a fourth dose of either BioNTech or Moderna vaccines. In mid-January, the head of the study, Gili Regev-Yochay, published the preliminary results: The fourth dose did increase the number of antibodies in both groups significantly, but probably not enough to prevent infections with the omicron variant.

Another Israeli analysis gave different results. The study compared 400,000 people over the age of 60 who had received a fourth vaccination with 600,000 people in the same age group who had had their third vaccination more than four months ago. According to the Israeli Ministry of Health, those who were boosted twice were three times better protected against serious illnesses. In addition, the protection against infection is twice as high as for those who have been vaccinated three times.

For whom can a fourth vaccination make sense and when?

Most experts recommend a more differentiated approach to the fourth vaccination than to the previous ones. For Ulrike Potzer, Director of the Institute for Virology at the Technical University of Munich, a fourth vaccination with the existing vaccines only makes sense for certain groups, such as immunocompromised people. “For many others, it might make more sense to wait and see.”

Leif Eric Sander, vaccine researcher at the Berlin Charité, also recommends a differentiated approach for the fourth vaccination, also with the vaccines adapted to Omicron. An adapted vaccine as a fourth vaccination would benefit, for example, older people who have an increased risk of a severe course of the disease and who also respond less well to vaccinations. He currently thinks little of a fourth vaccination for the entire population. “I think with three vaccinations you are super protected.”

In addition, large parts of the population would probably come into contact with the viruses and would thus automatically refresh their immune response. If future virus variants do not change the course of the pandemic, one might therefore only have to regularly vaccinate older people.

Why could a tailor-made fourth vaccination still be necessary for everyone?

At a press conference on the corona situation in mid-January, the virologist Christian Drosten said that a fourth vaccination with a vaccine adapted to Omicron could possibly be necessary for everyone. “We may have to update large parts of the population, maybe even all of them, against Omicron from the second quarter.”

His reasoning: The omicron virus is so different from the other corona variants that it belongs to a different group than all previous ones. The existing vaccine no longer fits. However, broad immunity against both groups is needed so that not only protection against serious diseases is given, but also protection against transmission and mild courses. In order to end the pandemic, large parts of the population must be immunized to such an extent that they can no longer transmit the virus. You would need the right vaccinations for that.

In the long run, you can’t vaccinate the entire population every few months, at some point the virus itself has to update people’s immunity again and again and build up protection against transmission.

Has the EMA issued a general warning about booster vaccinations?

Marco Cavaleri, responsible for the EMA’s vaccine strategy, recently caused a stir with statements about the fourth vaccination. Booster vaccinations every three or four months are not useful or sustainable, the immune system should not be “overloaded” with vaccinations. However, Cavaleri was only referring to booster vaccinations at these short intervals. He advocated annual booster shots. Experts also dispute the fact that booster vaccinations in quick succession could be counterproductive.

How should the fourth vaccination be assessed from a global perspective?

With a view to global vaccination equality, the World Health Organization has spoken out against blanket booster vaccinations. Director-General Tedros Ghebreyesus said at the end of December 2021 that nationwide booster campaigns would result in vaccine doses being delivered to countries that already have a high vaccination rate.

These cans were then missing in poorer countries. This would give the virus more room to spread and mutate, thus prolonging the pandemic rather than ending it. In addition, fewer deaths and serious illnesses would be prevented by booster vaccinations than by primary immunization.