Researchers have identified highly effective antibodies against the coronavirus SARS-CoV-2 and are now pursuing the development of a passive vaccination. In this process, they have also discovered that some SARS-CoV-2 antibodies bind to tissue samples from various organs, which could potentially trigger undesired side effects. They report their findings in the scientific journal "Cell".
Initially, the scientists isolated almost 600 different antibodies from the blood of individuals who had overcome COVID-19, the disease triggered by SARS-CoV-2. By means of laboratory tests, they were able to narrow this number down to a few antibodies that were particularly effective at binding to the virus.
Next, they produced these antibodies artificially using cell cultures. The identified so-called neutralizing antibodies bind to the virus, as crystallographic analysis reveals, and thus prevent the pathogen from entering cells and reproducing. In addition, virus recognition by antibodies helps immune cells to eliminate the pathogen.
Studies in hamsters - which, like humans, are susceptible to infection by SARS-CoV-2 - confirmed the high efficacy of the selected antibodies: "If the antibodies were given after an infection, the hamsters developed mild disease symptoms at most. If the antibodies were applied preventively - before infection - the animals did not get sick," said the coordinator of the current research project.
Treating infectious diseases with antibodies has a long history. For COVID-19, this approach is also being investigated through the administration of plasma derived from the blood of recovered patients. With the plasma, antibodies of donors are transferred. "Ideally, the most effective antibody is produced in a controlled manner on an industrial scale and in constant quality. This is the goal we are pursuing," said the first author of the current publication.
"Three of our antibodies are particularly promising for clinical development," explained, a research group leader. "Using these antibodies, we have started to develop a passive vaccination against SARS-CoV-2." Such a project requires cooperation with industrial partners. That is why the scientists are collaborating with Miltenyi Biotec.
In addition to the treatment of patients, preventive protection of healthy individuals who have had contact with infected persons is also a potential application. How long the protection lasts will have to be investigated in clinical studies. "This is because, unlike in active vaccination, passive vaccination involves the administration of ready-made antibodies, which are degraded after some time," the researcher said. In general, the protection provided by a passive vaccination is less persistent than that provided by an active vaccination. However, the effect of a passive vaccination is almost immediate, whereas with an active vaccination it has to build up first. "It would be best if both options were available so that a flexible response could be made depending on the situation."
During their investigations, the researchers made a further discovery: some of the particularly effective antibodies against the coronavirus specifically attached to proteins of the brain, heart muscle and blood vessels. In tests with tissue samples from mice, several of the neutralizing antibodies exhibited such a cross-reactivity. Thus, they were excluded from the development of a passive vaccination.
"These antibodies bind not only to the virus, but also to proteins in the body that have nothing to do with the virus. Future research is needed to analyse whether the associated tissues could potentially become targets of attacks by the own immune system," said the author. Whether these laboratory findings are relevant for humans cannot be predicted at present. "On the one hand, we need to be vigilant in order to detect any autoimmune reactions that may occur in the context of COVID-19 and vaccinations at an early stage. On the other hand, these findings can contribute to ensure the development of an even safer vaccine," the scientist said.
Highly effective antibodies against the coronavirus were identified
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