Highly effective antibodies against coronavirus identified
At the same time, they discovered that some SARS-CoV-2 antibodies also bind to tissue samples of various organs, which could possibly trigger undesired side effects. They are now reporting on these findings in the journal Cell*.
The researchers first isolated almost 600 different antibodies from the blood of people who had survived a COVID-19 disease caused by SARS-CoV-2. Laboratory tests enabled them to narrow down this number to a few particularly effective ones and then artificially reproduce them using cell cultures – in a Petri dish, so to speak. The so-called neutralising antibodies identified, as structural analyses show, bind to the virus, and thus prevent it from entering cells and multiplying. In addition, the detection of the virus by antibodies helps to eliminate the pathogen from immune cells. Studies on hamsters – which are similarly susceptible to infection by SARS-CoV-2 as humans – have shown the high effectiveness of the ultimately selected antibodies: „If the antibodies were administered after an infection, the hamsters developed mild disease symptoms at best. If the antibodies were administered preventively – before an infection – the animals did not become ill,“ says Dr. Jakob Kreye, coordinator of the current research project. The DZNE scientist is one of the two first authors of the current publication.
The treatment of infectious diseases with antibodies has a long history. For COVID-19, this approach is also being investigated in connection with the administration of plasma from the blood of recovered patients. The plasma is used to transfer antibodies from donors. „Ideally, the most effective antibody is produced in a targeted manner on an industrial scale and in consistent quality. That is the goal we are pursuing,“ says Dr. Momsen Reincke, also first author of the current paper.
„Three of the antibodies identified so far are particularly promising for clinical development,“ says Prof. Dr. Harald Prüß, research group leader at the DZNE and senior physician at the Clinic for Neurology with Experimental Neurology at the Charité. „Using these antibodies, we have now started to develop a passive vaccination against SARS-CoV-2“. This is only possible in cooperation with an industrial partner. Therefore, the researchers are working with the company Miltenyi Biotec.
In addition to the treatment of sick people, the precautionary protection of healthy people who have had contact with infected persons is also a possible application. How long the protection lasts has to be investigated in clinical studies: „Unlike active vaccination, passive vaccination involves the administration of ready-made antibodies which are broken down after a certain time,“ says Prof. Prüß. As a rule, the protection provided by passive vaccination is less stable than that provided by active vaccination. On the other hand, the effect of a passive vaccination is almost immediate, whereas with an active vaccination it has to build up first. „It would be ideal if there were both possibilities of vaccination so that we could react flexibly depending on the situation.
The team around Dr. Kreye, Dr. Reincke and Prof. Prüß usually deals with diseases of the brain and with antibodies that attack nerve cells by mistake. „In view of the COVID 19 pandemic, however, it was obvious to use our resources in other ways,“ says Prof. Prüß. For the current project, the researchers benefit from a Helmholtz Association funding project, the „BaoBab Innovation Lab“. In this project they are developing and refining technologies for the characterisation and production of antibodies, which they are now applying. „Now the task at hand is to work with our industrial partner to create the conditions that will enable us to produce the antibodies we have identified most effectively in large quantities,“ says Prof. Prüß. „The next step is clinical trials, i.e. testing on humans. This is not expected before the end of this year at the earliest. The planning for this has already begun“.
During the investigations, the researchers made an additional discovery: some of the particularly effective antibodies against the coronavirus specifically attached themselves to proteins of the brain, heart muscle and blood vessels. In tests with tissue samples from mice, several of the neutralising antibodies showed such cross-reactivity. They were therefore excluded from the development of 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. Further research will now have to examine whether the associated tissues could thus possibly become targets of attacks by the body’s own immune system,“ explains Prof. Prüß. Whether these laboratory findings are relevant for humans cannot be foreseen at present: „On the one hand, we must 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 may help to make the development of a vaccine even safer,“ he said.
For the current investigations, the DZNE research group led by Prof. Prüß cooperated closely with the Medical Clinic with a focus on infectiology and pneumology at the Charité and the Institute of Virology at the Charité Mitte campus. The Institutes of Virology and Veterinary Pathology of the Free University of Berlin and the Scripps Research Institute in the USA also played a major role.
*A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model, Jakob Kreye, S Momsen Reincke et al., Cell (2020), DOI: https://doi.org/10.1016/j.cell.2020.09.049
About the German Centre for Neurodegenerative Diseases (DZNE)
The DZNE researches all aspects of neurodegenerative diseases (such as Alzheimer’s, Parkinson’s, and ALS) in order to develop new approaches to prevention, therapy and patient care. Through its ten locations, it bundles nationwide expertise within one research organisation. The DZNE cooperates closely with universities, university hospitals and other institutions at national and international level. The DZNE is a member of the Helmholtz Association.
About Charité – University Medicine Berlin
The Charité – Universitätsmedizin Berlin is one of the largest university clinics in Europe with around 100 clinics and institutes on 4 campuses and 3,001 beds. Research, teaching, and patient care are closely interlinked here. With an average of around 15,500 employees at the Charité and 18,700 employees from over 100 nations, Berlin University Medicine is one of the largest employers in the capital. Of these, 4,553 were employed in the nursing sector and 4,454 in the scientific and medical fields. At the Charité, 154,261 full and part-time inpatient cases and 700,819 outpatient cases were treated last year. In 2019, the Charité will have total revenues of around 2.0 billion euros, including third-party funding and investment grants. With the 179.1 million euros in third-party funds raised, the Charité achieved a new record. More than 8,000 students are trained in human medicine, dentistry, and health sciences at the medical faculty, which is one of the largest in Germany. In addition, there are 644 training places in 9 health professions