A research team at Ulm University Medical Center has discovered protein impurities in the Covid 19 vaccine from the British-Swedish manufacturer AstraZeneca. So far, the researchers do not believe that they affect efficacy or that there is a link to vaccine reactions.The study has been published as a preprint, and peer review is pending. The study is going through the review process at a journal in the Nature Portfolio family of journals.

The research team describes results of a quantitative comparison of protein components between the whole vaccine and a purified adenovector. This is the carrier virus that introduces the genetic components of Sars-Cov-2 into the body cells of vaccinated individuals and triggers the immune response against the coronavirus.Three batches of the vaccine studied contained more protein components than could be accounted for by the vector alone. Among them are heat shock proteins, which are involved in protein folding and stabilization in the body, for example, when cells are exposed to a high temperature or an infection is present.

In total, more than 1,000 different proteins were detected in the three batches studied, he said. Most of them are unlikely to have negative effects on vaccinated individuals, said study leader Stefan Kochanek: "However, extracellular heat shock proteins are known to modulate innate and acquired immune responses and can amplify existing inflammatory responses." They have also been linked to autoimmune responses, he said.The presence of the proteins points to deficiencies in quality control, Kochanek says. Revising the manufacturing process and quality control could possibly increase the vaccine's efficacy as well as safety. AstraZeneca's vector vaccine is produced by multiplying the adenovirus in human cells and then purifying it as best as possible from other cell components.

Theoretical connections to cerebral vein thrombosis

"It's perfectly normal to find protein components in vaccines," said Andreas Greinacher of Greifswald University Medical Center. The amount appears to be relatively high in the AstraZeneca vaccine, he said. "As far as the human proteins are concerned, we are just beginning to understand to what extent they might also be involved in complex formation," the immunologist said of the possible connection with cerebral venous thrombosis, which has occurred in rare cases after vaccination with the vaccine. "This is not far-fetched, but it needs further investigation," Greinacher says.

"It is not yet clear whether the described byproducts have any relevance to the immune response or the rare side effects," says Leif-Erik Sander, a vaccine researcher at Charité University Medicine Berlin. The strong immune response that many experience after the first dose with the vaccine is likely triggered by the vaccine viruses, he said.

Greinacher believes it is possible that the proteins found in the vaccine set in motion a chain of reactions that occur in the development of cerebral venous thrombosis: "They provide a short-term immune response, which causes a warning signal that triggers an autoimmune reaction." In the process, the highly reactive autoantibodies led to the rare thromboses in the few people who experienced these side effects.

Purification and vaccine losses

"It now needs to be investigated whether further purification of the vaccine will, on the one hand, reduce the harmless but unpleasant acute vaccine reactions, but more importantly, whether it can reduce the severe complications," Greinacher says.Stephan Becker, a virologist at Philipps University in Marburg, also recommends removing superfluous proteins during the purification of vaccines, but he says that some of the viral proteins are always lost in the process. This also affects the amount of vaccine available. Becker has no concerns about the proteins. He said the study describes a condition that is "pretty normal."

Image by Paul McManus