COVID-19: Berlin scientists lay basis for a passive vaccination
Highly effective antibodies against the coronavirus were identified

Date:
September 24, 2020
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
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.



FULL STORY ========================================================================== Researchers at the German Center for Neurodegenerative Diseases (DZNE)
and Charite' -- Universita"tsmedizin Berlin 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 Dr. Jakob Kreye, coordinator of the current research project.

The DZNE scientist is one of the two first authors of the current
publication.

Antibodies for passive vaccination 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 Dr. Momsen Reincke, also first author
of the current publication.

"Three of our antibodies are particularly promising for clinical
development," explained Prof. Dr. Harald Pru"ss, a research group leader
at the DZNE and also a senior physician at the Clinic for Neurology
with Experimental Neurology at Charite' -- Universita"tsmedizin
Berlin. "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," Prof. Pru"ss
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." Modern technologies Kreye, Reincke,
Pru"ss and colleagues usually deal with autoimmune diseases of the
brain, in which antibodies erroneously attack neurons. "In the face of
the COVID-19 pandemic, however, it was obvious to use our resources
also in other ways," said Prof. Pru"ss. For the current project, the researchers benefit from a project funded by the Helmholtz Association:
the "BaoBab Innovation Lab." Within this framework, they are developing
and refining technologies for the characterization and production of antibodies, which they are now applying.

"Now, we are working with our industrial partner to establish the
conditions that will allow for the most effective large-scale production
of the antibodies we have identified," said Pru"ss. "The next step is
clinical trials, that is testing in humans. However, this can not be
expected before the end of this year at the earliest. The planning
for this has already started." Potential side effects 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 Prof. Pru"ss. 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.

Partners in research For the current studies, the DZNE research group lead
by Prof. Pru"ss collaborated closely with the Department of Infectious
Diseases and Respiratory Medicine at the Charite' and the Institute of
Virology at the Campus Charite' Mitte. The Institutes of Virology and Veterinary Pathology at the Freie Universita"t Berlin and the Scripps
Research Institute in the US were also significantly involved.


========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jakob Kreye, S. Momsen Reincke, Hans-Christian Kornau, Elisa
Sa'nchez-
Sendin, Victor Max Corman, Hejun Liu, Meng Yuan, Nicholas C. Wu,
Xueyong Zhu, Chang-Chun D. Lee, Jakob Trimpert, Markus Ho"ltje,
Kristina Dietert, Laura Sto"ffler, Niels von Wardenburg, Scott van
Hoof, Marie A. Homeyer, Julius Hoffmann, Azza Abdelgawad, Achim
D. Gruber, Luca D. Bertzbach, Daria Vladimirova, Lucie Y. Li,
Paula Charlotte Barthel, Karl Skriner, Andreas C. Hocke, Stefan
Hippenstiel, Martin Witzenrath, Norbert Suttorp, Florian Kurth,
Christiana Franke, Matthias Endres, Dietmar Schmitz, Lara Maria
Jeworowski, Anja Richter, Marie Luisa Schmidt, Tatjana Schwarz,
Marcel Alexander Mu"ller, Christian Drosten, Daniel Wendisch,
Leif E.

Sander, Nikolaus Osterrieder, Ian A. Wilson, Harald Pru"ss. A
therapeutic non-self-reactive SARS-CoV-2 antibody protects from
lung pathology in a COVID-19 hamster model. Cell, 2020; DOI:
10.1016/j.cell.2020.09.049 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200924135401.htm

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