From what age is a fourth vaccination advisable? Are other boosters also good for younger people or do they even tire the immune system? Scientifically, these questions have not yet been clearly clarified, as assessments by four experts show. US figures give indications of a possible age limit.
The communication from the responsible authorities on the question of who should receive a second booster vaccination is more than unfortunate. While the Standing Vaccination Commission (STIKO) has so far only advised those over 70 and those with previous illnesses to take the fourth dose, Federal Minister of Health Lauterbach also recommends those under 60 for a second booster. The European Medicines Agency EMA and the EU health authority ECDC are in between, they advocate a fourth dose from the age of 60.
That looks like arbitrary age limits, but the sometimes harsh criticism of those responsible is not entirely justified. Because even in science there is apparently still no consensus on how exactly booster vaccinations affect the immune system and whether they have a positive effect at all in younger people. This is shown by statements given by four experts to the Science Media Center. However, even in these assessments, the role of vaccine breakthroughs is at best indirectly included.
Onur Boyman, Director of the Clinic for Immunology at the University Hospital Zurich, has a very clear opinion on boosters. "Booster vaccinations against Sars-CoV-2 lead to a quantitative and qualitative improvement in immune memory against the virus," he says. "The former is reflected, for example, in the increase in Sars-CoV-2-specific antibody levels after vaccination. This in turn leads to a resumption of high antibody levels in the blood and mucous membranes where the virus invades, as antibody levels in these locations decrease over time lose weight." The qualitative improvement is shown by the broadening immune response against Sars-CoV-2, which also entails better protection against new variants.
Andreas Thiel, head of the Regenerative Immunology and Aging working group at the Berlin Institute of Health of the Berlin Charité, only considers the fourth dose to be an actual booster. "The previous third vaccination should be regarded as a completely normal last vaccination of a basic scheme," he says. "Many studies - including our own - show very clearly that the third vaccination is also a must for younger people in order to induce longer-lasting antibody titers. Studies from Israel and Great Britain also show a large-scale effect on the severe courses, especially in Elderly demonstrated."
Andreas Radbruch, Scientific Director of the German Rheumatism Research Center Berlin (DRFZ), considers a fourth vaccination and further boosters to be of little use. "The immunological memory increases its long-term antibody production after each new provocation until it has become accustomed to this antigen in this dose in this way," he says. It is then "satisfied".
If the vaccine is administered systemically, the antibodies intercept the antigen before it can trigger another immune response. Studies indicated that vaccinated people who had good immunity after just three doses no longer responded to the fourth dose.
According to Radbruch, protection against serious illness and death is already given after the second vaccination in 90 percent and after the third in 94 percent in the long term and also against Omikron. If so, then a fourth vaccination would only make sense for older people. And there you could discuss whether from 60 or 70 or 80 years.
Ultimately, regardless of age, you have to look at how a person responded to the first three vaccinations, he says. From an immunological point of view, it would be responsible to detect serologically at-risk patients who would not have reacted and to protect them passively prophylactically with antibody preparations.
Christian Bogdan, Director of the Microbiological Institute at the University Hospital Erlangen and member of the Standing Vaccination Committee, sees it similarly. "The only purpose of the Covid-19 vaccination is to prevent serious Sars-CoV-2 infections, hospitalization and death as a result of Covid-19," he says. "For immunocompetent people without previous illnesses, this goal is achieved with three vaccinations for the virus variants currently circulating. Further vaccinations do not currently bring any additional benefit in this group of people."
"The situation is different for immunocompromised people - for example elderly people and people with tumor diseases or transplants - who may not develop sufficient protection after three vaccinations. A fourth vaccination is advisable here in any case, as already recommended by the STIKO in January 2022 recommended."
In order to avoid saturation of the immune system, Bogdan points out that booster vaccinations should be given well after the second vaccination, ideally no earlier than after six months. If you vaccinate into a previous immune response that is still ongoing, this effect is greatly weakened, since antigens produced as a result are quickly intercepted. "The motto that a lot helps a lot doesn't apply to vaccination."
Onur Boyman considers a possible saturation of the immune system to be very theoretical and not consistent with clinical experience. "The claims that more booster shots would 'saturate' the immune system or that more or fewer booster shots are better or worse are not correct," he says. These aspects must be looked at individually, which means that people who are at increased risk of developing severe Covid 19 disease, for example due to their old age or an immune deficiency, can benefit from more frequent booster vaccinations."
Andreas Thiel sees no problem at all in a possible saturation of the immune system: "When immune protection decreases, the immune memory is reactivated by a booster vaccination. If there is still sufficient protection, this activation decreases accordingly."
Immunological risks of repeated boosters are not yet known, says Thiel. For example, smallpox vaccinations are sometimes mandatory annually for employees of high-security laboratories in the USA or Germany. "There are no negative effects here."
Andreas Radbruch contradicts this thesis. Repeated useless boosters have several risks, even if the antibody-producing adaptive immune system no longer kicks in, he says. "While the benefit of the fourth vaccination is manageable, 80 percent of those vaccinated reacted with local side effects and 40 percent with systemic side effects," which is at least unpleasant, he says.
More problematic is that intolerance to future vaccines with a similar structure could arise. It should also be checked whether autoimmune diseases could develop, says Radbruch. He also doesn't rule out the possibility that excessive boosting could lead to what is known as Original Antigenic Sin. There are first indications that a strong immunity against a certain variant of the virus shapes the immune system in such a way that it reacts poorly to a new variant. This effect could possibly also occur due to too many "blind" boosters, he says.
"There have so far been no comprehensive immunological studies for the Sars-CoV-2 vaccines on the question of the possible harm of additional vaccinations that are not clinically indicated," says Christian Bogdan. "Basically, a second booster vaccination, i.e. a fourth vaccination, is well tolerated in terms of local or systemic normal vaccination reactions. The immunological effect of repetitive mRNA vaccinations is currently being intensively researched."
-> The detailed statements of the scientists with references can be read at the SMC.
So many questions are still open. Figures from the US health authority CDC show that booster vaccinations generally increase protection against serious illnesses and death. In May, the risk of dying from Covid-19 in the United States was about 24 times higher for unvaccinated over-50s than for their peers who had been boosted once. People with a fourth dose had an approximately four times lower risk compared to this group.
However, a basic recommendation for a second booster from the age of 50 cannot be derived from this, since theoretically only people over 60 or 70 years of age who were vaccinated three times could have died and not younger people. If you switch to CDC statistics by age group, this appears to be the case as well.
Because here you can see that the incidence among unvaccinated 50 to 64 year olds on May 22 was only 0.81. In the over 65-year-olds, on the other hand, it was 9.14 for unprotected people and 1.38 and 1.03 for those who had basic immunization or who had been boosted once. Those who were vaccinated four times were not included in these statistics.
The effect on the incidence is generally rather small due to the second booster. For the unvaccinated, it was 5.49 deaths per 100,000 population on May 22, for those over 50 years of age who were unvaccinated. For those who boosted once, it was only 0.72; 0.23 for four times vaccinated. A basic immunization with two doses, on the other hand, already showed a large effect, with an incidence of 0.92 in this group.
The small difference is probably mainly due to the spread of the milder omicron variant. Because in winter the gap was significantly higher. On June 2, 23.29 unvaccinated died per 100,000 population; 3.03 basic immunized and 1.16 boosted.
