Corona vaccination: What the Stiko recommendation for Astra Zeneca means

After the delta variant of the coronavirus is also spreading rapidly in Germany, the Standing Vaccination Commission (Stiko) adjusted its vaccination recommendation on Thursday. People who have already received a first injection with the preparation from Astra Zeneca are now advised to have a second vaccination with an mRNA vaccine from Biontech or Moderna – regardless of age. What findings led to the amended recommendation, and what do those affected now need to know?

Why did Stiko change its recommendation?

The occasion is a long-awaited publication by a British research group led by Matthew Snape from Oxford University. With the help of 830 test persons, the scientists examined which sequence of vaccines from Astra Zeneca and Biontech elicits which immune response against the coronavirus. Stiko took these results as an opportunity to revise its recommendation. It has been shown that the so-called heterologous vaccination from a first vaccination with Astra Zeneca and the second vaccination with Biontechs Comirnaty leads to a “clearly superior” immune response compared to a double vaccination with Astra Zeneca. The Stiko announced on Thursday. Since the Biontech and Moderna vaccines are similar in principle, it is assumed that Moderna can also be used for the second syringe instead of Biontech.

What was the rule before?

Due to very rare but serious cases of blood clots in the brain (so-called cerebral vein thrombosis), especially in younger people, the Stiko had recommended on March 31 that the Astra-Zeneca vaccine should only be administered to people over 60. People under the age of 60 who had already received a first vaccination with the drug from Astra Zeneca, had advised the Stiko to have a second vaccination with the vaccine from Biontech or Moderna. Now this recommendation applies regardless of age. At that time, unlike now, the decision was not justified with a better immune response after the injection of two different active substances. Reliable study results on this were not yet available at this point in time.

Should patients who have an appointment for a second vaccination with the Astra-Zeneca vaccine reschedule now?

Health Minister Jens Spahn (CDU) said at a press conference on Friday that the new recommendation could already be implemented wherever sufficient mRNA vaccine is available. This is not yet the case in all vaccination centers and practices and will probably take a few more days. Vaccinated persons can still opt for a second vaccination with the Astra-Zeneca vaccine. The double vaccination with it is also effective and safe.

The new recommendation applies “subject to the feedback from the comment procedure, which has yet to be opened,” it said. What does that mean?

When Stiko makes a decision, it presents it to various scientific and medical societies that deal with the subject. In this case, for example, the German Society for Immunology and the German Society for Pneumology and Respiratory Medicine. They have the opportunity to provide comments and comments. If you raise technical objections, Stiko will advise you and possibly adjust your recommendation. The commenting process takes about two days. The publication of the recommendation and the scientific justification is expected in the coming week.

How do the vaccines from Astra Zeneca, Biontech and Moderna differ?

There are different types of Covid-19 vaccines. All vaccines train the immune system so that it can quickly recognize and fight the coronavirus in the event of an infection. Almost all vaccines present the body with the spike protein, which the coronavirus wears like a crown on its surface. With the help of the spike protein, the virus binds to human body cells and attacks them. If the human immune system turns against this protein, it can prevent the virus from infecting body cells and render the virus harmless.

The construction of the various vaccines differs considerably from one another. The Astra Zeneca vaccine is a vector vaccine based on a virus. The gene for the spike protein has been inserted into this. The viruses only serve as vehicles (vectors) to bring this important message into the human cells. The cells then use the genetic information contained in the vaccine to produce the protein of the coronavirus and thus mobilize the immune system.

The preparations from Biontech and Moderna are mRNA vaccines. In this approach, humans are not injected with an inactivated virus to stimulate the immune system, but rather a piece of mRNA that contains the assembly instructions for the spike protein of the coronavirus.

Why is a combination of both active ingredients apparently more effective than two vaccinations with the Astra Zeneca vector vaccine?

The two vaccines trigger slightly different immune responses. The Biontech vaccine leads to a somewhat stronger production of antibodies than the Astra-Zeneca vaccine. Instead, the latter leads to the formation of more T cells. Both immune responses are important in fighting the coronavirus. A combination therefore leads to a “particularly strong immune response”, as Christine Falk, President of the German Society for Immunology, says. However, the order is not indifferent. First Biontech and then Astra did not achieve such good results in the Oxford study. The T-cell help has to come first, says Falk.

Is the protection even greater enough after two vaccinations with Astra Zeneca?

Yes. Usually there is nothing to worry about if you have already received this vaccination. “Stiko recommends cross-vaccination now because it is better than vaccination with just Astra,” says immunology professor Carsten Watzl from TU Dortmund. “That doesn’t mean that double vaccination with Astra is bad.” Data from Great Britain, where Astra Zeneca is primarily vaccinated, shows that the protection afforded by this vaccine against severe disease and death is still excellent – also against the highly contagious Delta variant. For people with a particularly weak immune system such as very old people, organ transplants or cancer patients, a third vaccination with an mRNA vaccine could be useful, says immunologist Christine Falk. Whether you have reacted well enough to the vaccination can be checked with the help of a special antibody test at your family doctor, says Falk.

Does that make the Astra Zeneca vaccine worthless?

No that’s not him. The vaccine could even become particularly important as a primary vaccination in combination with Biontech or Moderna. Because the combination is at least equivalent to the double vaccination with Biontech, if not slightly superior. “The sequence Astra and then Biontech is a really good strategy,” says Christine Falk, “at least as good as twice Biontech.” It should also be borne in mind that in the Oxford study, the vaccination interval for all combinations was only four weeks. The double vaccination with Astra Zeneca unfolds its highest potential, however, with an interval of nine to twelve weeks. If this distance had been examined, the double Astra-Zeneca vaccination would have been better. In view of the spread of the delta variant, against which the first vaccination, unlike earlier variants, does not offer good protection, a particularly fast double vaccination is important, which has also prompted Stiko to change its recommendation.

How tolerable is the combined vaccination?

According to several studies, the combined vaccination is considered to be well tolerated. According to the interim evaluation of a study by the immunologist Leif Erik Sander from the Berlin Charité, the vaccination reactions were comparable in two groups, one of which had received the Biontech vaccine twice and the other first Astra Zeneca and then Biontech. A large number of test subjects, regardless of which group they belonged to, reported mild to moderate local vaccination reactions such as pain in the arm or flu-like symptoms. In an earlier study by the team from Oxford, however, the combination vaccination led to flu-like symptoms a little more frequently – probably because the interval here was four weeks, says Carsten Watzl. “Serious side effects are not known for the combination,” says the immunologist. No unpleasant surprises are to be expected here, because it is not a question of a simultaneous combination of two drugs. “If you come with the second vaccine after four weeks, the first one is long gone. It is therefore not to be expected that this will lead to new side effects that we are not yet aware of.”

What time intervals should be observed between the first and second vaccination?

Stiko recommends an interval of at least four weeks for people who are immunized with two different vaccines. According to the Federal Minister of Health Jens Spahn (CDU), the combined vaccination offers very good vaccination protection with a high level of effectiveness after just four weeks. As a result, the very long interval of up to twelve weeks, which was previously applicable, can be shortened. In the homologous vaccination schedule, i.e. if the same active ingredient is injected for the first and second vaccination, different recommendations apply. With the Biontech vaccine, there should be three to six weeks between the first and second injection, four to six weeks for Moderna and nine to twelve weeks for Astra Zeneca, if someone else is vaccinated twice with it.