Rescue protection for the chronically ill and other risk groups?
by Michael Wichert
(17.12.2020) The Deutsche Herzstiftung eV supports the development of new antibodies as a therapy against Covid-19. An active ingredient candidate from researchers at the TU Braunschweig is already entering the clinical phase as a prophylaxis option for vaccination for the chronically ill and medical professionals. An application of the first vaccine candidates to people to protect against Covid-19 is imminent.
The small tube shown by Prof. Stefan Dübel (TU Braunschweig) contains the blueprints of billions of different antibodies from all over the world. Such gene libraries are the starting point for the development of new antibody therapies.
Photo: Jörn Josewski / TU Braunschweig
How the COR-101 antibody works against the SARS-CoV-2 virus.
Photo: Stefan Dübel / CORAT Therapeutics GmbH
Typical “active” vaccines do not cure the disease. Before they come into contact with the pathogen, they have to trigger an immune response in the body that is accompanied by the formation of protective antibodies. “The vaccination to protect against the ‘normal’ flu has a great and proven benefit, especially for heart patients”, emphasizes heart specialist Prof. Dr. Heribert Schunkert from the board of the German Heart Foundation as part of the Covid 19 project funding of the Heart Foundation.
The effect of a vaccination only occurs after two to three weeks. However, this period of time is too long for patients with a severe acute Covid-19 disease or for medical nursing staff who should be protected immediately. In addition to vaccines, antibody therapies (“passive” vaccines) should therefore also be used to protect healthy people from Covid-19 disease or to support the immune system of people with Covid-19. You could directly neutralize the virus.
Human antibodies produced in the laboratory have the advantage that they protect the body against infection by the coronavirus within minutes to a few hours through passive immunization, depending on the dose (intravenous, subcutaneous) – until the immune system has produced its own antibodies.
Protect the elderly and the chronically ill from Covid-19
This is exactly where the research project “Human monoclonal antibodies against SARS-CoV-2 for prophylaxis against Covid-19 – development support” at the Technical University of Braunschweig comes in, financially funded by the German Heart Foundation with 50,000 euros. The goal of developing a drug against Covid-19 should be not only to support the healing process of those with acute Covid-19, but also to protect risk groups from infection who cannot benefit one hundred percent from a corona vaccination: people with previous illnesses and older people.
The administration of antibodies can therefore be an important therapeutic addition to the vaccination against Covid-19. In Germany, millions of people are among the population groups who are often unable to develop their own immune activity against viruses such as SARS-CoV-2 quickly enough: In addition to the elderly, these include, in particular, chronically ill people with cancer, cardiovascular diseases, congenital heart defects, patients after one Organ transplants with weakened immune activity or patients with kidney or lung diseases.
Replicated human antibodies against Covid-19 from the test tube
A network of scientists led by molecular biologist Prof. Dr. In April 2020, Stefan Dübel from the Technical University (TU) Braunschweig succeeded in producing the first human antibody (COR-101) against SARS-CoV-2 in a test tube. The approximately 80 scientists in the so-called “Corona Antibody Team” (CORAT), a consortium from the Institute for Biochemistry, Biotechnology and Bioinformatics at the TU Braunschweig, which Prof. Dübel heads together with his colleague Prof. Michael Hust, together with the biotechnology company Yumab GmbH and many other supporters have recreated the monoclonal antibody COR-101 according to the genetic blueprint, the DNA sequence, of human antibodies taken from the bloodstream of healthy people. “These antibodies are indistinguishable from antibodies in our own body, except that they can block the coronavirus,” explains Dübel.
Clinical studies are now to test the effectiveness of COR-101 on humans in a greatly shortened procedure – also approved by the licensing authorities. First, the new active ingredient is carefully tested for side effects, as Dübel emphasizes. “Experience has shown that human antibodies have a significantly more tolerable side effect profile than chemical substances – after all, everyone else always has them in large quantities in their own blood.”
Mechanism of action against SARS-CoV-2 clarified
The antibody reproduced by CORAT works according to a very simple principle. It targets a surface anchor on the protein envelope of SARS-CoV-2, the virus surface spike protein with which the virus docks to the human cell. The antibody blocks the spike protein and thus prevents the virus from docking and thus penetrating the cell: the human organism is protected against an outbreak of Covid-19.
The clinical application of this neutralizing antibody candidate is intended to focus on those patients who cannot be treated with vaccination. “We expect that the antibody can also protect healthy people, i.e. people not yet suffering from Covid-19, from coronavirus infection,” said Dübel. Based on experience with other antibody drugs, the duration of action should be around one to three months.
Antibody production in cell power plants: large quantities, constant quality
The Braunschweig scientists have found their “antibody super-candidate” in gene libraries with around ten billion human antibody gene construction plans. The gene libraries are obtained from immune cells in human blood from donors, including recovered Covid-19 patients. A person’s entire antibody repertoire fits into a small test tube. In a large number of tests running in parallel, the ideal antibody-drug candidate had to qualify not only to be effective against SARS-CoV-2, but also to have good storage properties and be easily producible. He also recognizes new variants (mutants) of the virus that have emerged in the meantime.
Antibody method already proven in virus control
Dübel and his CORAT colleagues generated the SARS-CoV-2 neutralizing antibody with the help of the so-called antibody phage display. This procedure, which was developed by researchers at the TU Braunschweig before Corona, had already proven itself with many other viruses, including the dangerous Marburg virus or the Sudan Ebola virus.
“In this process, human monoclonal antibodies from human blood, that is, those derived from a single cell clone, are captured on the surface of a phage, a type of transport virus,” explains Prof. Dübel in the TU Braunschweig magazine. “The advantage of the method is that antibodies against any substance can be found in the shortest possible time, because there is no dependency on plasma donors,” emphasizes the researcher. In addition, when people donate plasma, the quality of the antibodies always varies, and not enough can be obtained to treat all the sick.
This was also made clear in a clinical study that could not show any benefit from a serum made from antibodies from Covid-19 convalescents.In contrast, artificially produced but genetically completely human antibodies based on the method of the Braunschweig researchers in the CORAT group are always precisely known The composition and quality of the antibodies are guaranteed, and they can be produced in any quantity.
Easier application of antibodies
Dübel also emphasizes another advantage of antibodies: “In contrast to the RNA vaccines currently being approved, antibody drugs do not require sophisticated freezer logistics because they are very stable and robust molecules”. A century ago, according to the molecular biologist, doctors carried around unrefrigerated bottles with antibodies in their pockets for weeks, so that they were always ready for use against tetanus or diphtheria, for example. “I therefore expect much simpler and cheaper logistics for COR-101 than for the RNA vaccines currently being developed. We also need much fewer doses compared to these vaccines, since we only have to treat infected and risk groups. “
The German Heart Foundation’s Covid 19 research funding
The pandemic caused by the novel coronavirus SARS-CoV-2 is associated with high risks for people with cardiovascular diseases and congenital heart defects. For many Covid-19 sufferers, the consequences for the heart and other organs are serious, including long-term impairment of heart and lung function. With the aim of helping to clarify the most urgent questions about the novel coronavirus in connection with cardiovascular diseases and congenital heart defects as quickly as possible, the German Heart Foundation has set up an ad hoc initiative to fund research in the fight against SARS-CoV -2 provided.
Out of a total of 60 research proposals, 14 research projects were selected for project funding with a total funding volume of over 940,000 euros. “In an extreme situation such as the pandemic caused by the novel coronavirus, new research results are extremely important to improve prevention and treatment,” emphasizes the emergency physician and cardiologist Prof. Dr. med. Dietrich Andresen, chairman of the board of the German Heart Foundation.
His deputy on the Board of Directors of the Heart Foundation, Prof. Dr. med. Thomas Voigtländer adds “With the funding we want to gain reliable knowledge in diagnostics and therapy as quickly as possible on the basis of top-class research that will help protect cardiovascular patients from the consequences of Covid-19 disease.”