AstraZeneca and BioNTech: a good combination?
Maximilian Reindl studied chemistry and biochemistry at the LMU in Munich and has been a member of the editorial team since December 2020. He will familiarize himself with medical, scientific and health policy topics for you in order to make them understandable and comprehensible.
More posts by Maximilian Reindl All content is checked by medical journalists.For a long time, experts have been discussing whether a combination of different coronavirus vaccines might provide better protection against the Covid-19 disease. The discussion has recently gained further momentum: the STIKO recommends under 60-year-olds who have received the first dose of the AstraZeneca vector vaccine a second vaccination with an mRNA vaccine. But how effective and how safe is such a “cross-vaccination”? Find out here what is known - and what is not.
Why is cross vaccination being discussed?
Combining coronavirus vaccines has been discussed by researchers and medical professionals for a long time. The main focus was on an adapted vaccination strategy against new virus variants. The hypothesis: Different combined vaccines could provide better protection against emerging newer coronavirus variants.
This previously purely technical discussion is now having practical consequences faster than expected. The Standing Vaccination Commission (STIKO) amended its vaccination recommendation on May 12, 2021: People who have already been vaccinated once with the AstraZeneca preparation and are younger than 60 years should receive an mRNA vaccine instead of the second dose of VaxZevria.
Why is there an adapted recommendation from STIKO?
The background for the decision of the STIKO were reports of (very) rare serious side effects of the vector vaccine VaxZevria. These are cerebral vein thromboses, which can also be associated with a lack of blood platelets.
From a purely immunological point of view, the approach of cross-vaccination is plausible, according to the STIKO experts: Both the vector vaccines approved to date and the mRNA vaccines train the immune system for the same target antigen of the Sars-CoV-2 pathogen (spike protein).
Who does the STIKO recommendation affect?
This recommendation affects many people in Germany: As of April 30, 2021, according to the Paul Ehrlich Institute, around 5.7 million people in Germany had already been vaccinated once with the AstraZeneca preparation. Of these vaccinees, only around 44,000 people completed the vaccination series with a second VaxZevria vaccination.
These figures also include older people over 60 years of age. Nevertheless, the updated recommendation of the STIKO affects a large number of young and younger people who are now faced with the question: Which second vaccination is best for me to get full protection against Covid-19?
How Safe and Effective is Cross Vaccination?
The study situation is still thin. Certain empirical values with similar vaccination approaches exist, for example, with vaccines against the Ebola virus. However, how effective and how safe a combined series of vaccines with the AstraZeneca vaccine VaxZevria and a second dose of the BioNTech vaccine Comirnaty is, experts are not yet able to conclusively assess.
Animal model studies
Initial studies in animal models provide some information on the effects of cross-vaccinations. This indicates that the different vaccines activate the animals' immune system in slightly different ways: VaxZevria produced a stronger T-cell immune response in mice, while Comirnaty produced more pronounced “antibody responses”.
These complementary properties of the two preparations could represent an advantage in protecting against Covid 19 disease. However, such animal experiments cannot simply be transferred to humans. Only clinical studies show how the combined vaccination works in humans.
The Spanish Combivacs study
The so-called Combivacs study by the Instituto de Salud Carlos III in Madrid received a lot of media attention: According to preliminary results, the combined vaccine administration should increase the amount of neutralizing antibodies sharply after the second vaccination with Comirnaty - a clear indication of protective immunity.
In order to better classify these results, however, it is necessary to take a look at the study protocol: First of all, it is a phase II study that serves as a “proof of concept”. This means that it only examines the question of whether the combined vaccine administration has a positive effect on the immune response.
The Combivacs study included around 600 study participants who had already received an initial vaccination with the AstraZeneca preparation. This collective of patients was divided into two groups: One included around 400 participants, the other around 200 people.
The larger group received the BioNTech vaccine Comirnaty as a second vaccination within eight weeks. The participants in the control group, however, remained unvaccinated. So they did not receive a second vaccination, as is provided for in a regular series of vaccinations with VaxZevria.
The Combivacs study therefore does not provide any information on whether a regular vaccination series - consisting of two doses of VaxZevria (homologous vaccination series) - is better or worse than cross-vaccination. The study therefore does not answer which of the two approaches for first-time vaccination with Vaxzevria is the more effective option.
The patient population is also quite small. Conclusions about possibly occurring (very) rare side effects are not possible.
The Oxford University Com-COV Study
British researchers have been testing the combination of vaccines from BioNTech and AstraZeneca since the beginning of February. The so-called Com-COV study by the University of Oxford is intended to shed light on the safety of a possible cross-vaccination.
The first interim results were published on May 18, 2021 in the journal “The Lancet”. Around 800 people took part, who on average were over 50 years of age.
They were divided into four groups:
- One group received first VaxZevria, then Comirnaty (heterologous).
- The second group received Comirnaty, then VaxZevria (heterolg).
- The third group received (regularly) two comirnaty (homologous).
- The fourth group received VaxZevria (homologous) twice.
Test subjects who received a cross-vaccination (heterologous vaccination schedule) reported, in some cases, stronger vaccination reactions after the second vaccination than participants in the homologous vaccination schedule. Fatigue, headache, joint pain, malaise and pain at the injection site could therefore occur more frequently as a result of a vaccine change.
The authors emphasize that these vaccination reactions were only temporary in the context of the study. The administration of paracetamol after the vaccination alleviated the symptoms. The scientists are currently not yet able to conclusively assess how safe a heterologous vaccination schedule actually is. Further data and results are announced for June this year.
What other practical advantages could cross-vaccination bring?
In addition to safety aspects, there are organizational questions: Could cross-vaccinations - also known as the “mix-and-match approach” - be beneficial in order to cushion possible future vaccine shortages?
If such a vaccination scheme turns out to be beneficial, doctors could make vaccine allocation more flexible in the ongoing vaccination campaign. If there is a temporary shortage of a vaccine, doctors could easily switch to an alternative coronavirus vaccine to complete a series of vaccinations. This may speed up the vaccination campaign.
Why do you need booster vaccinations?
Second vaccinations are supposed to "strengthen" the immunological memory. The renewed stimulus again provokes an immune response. This is usually much stronger than after the first vaccination, as the immune system already knows how to react. The second vaccination is especially important for those for whom the first vaccination was less effective or not at all (e.g. due to incorrect administration).
However, a double vaccination is not always absolutely necessary, as the example of the Johnson & Johnson vaccine shows. According to the registration documents submitted, a booster vaccination does not have any significant advantages over a single dose.
So whether a second vaccination makes sense or not depends largely on the vaccine used and the results of the approval studies.
