5.6.2020 - CORAT publishes the first substantial dataset describing fully human antibodies from heathly donors that are able to block the infection by SARS-CoV-2. Preprint in bioRxiv: doi: 10.1101/2020.06.05.135921
Fighting COVID19 with recombinant fully human Antibodies neutralizing SARS-CoV2
CORAT is a consortium of academic and industrial partners with the mutual goal to develop a passive vaccination immunotherapy against COVID-19 employing novel fully human monoclonal antibodies neutralizing SARS-CoV2.
A large set of more than 750 human monoclonal antibodies recognizing SARS-CoV2 Spike (S) protein has already been isolated by antibody phage display from human antibody libraries from healthy donors and convalescent COVID-19 patients. These antibody candidates currently undergo a fast track development process to identify lead molecules with optimal drug features for a passive vaccine. Innovative and state of the art methods are used to manufacture the drug candidate in much shorter time than ever done so far while keeping all necessary safety and quality requirements for medical use substances. We will generate materials ready to be evaluated in clinical studies as immunotherapy to treat acute COVID-19. Moreover, this drug candidate may also be applied in a prophylactic scheme to protect medical care personnel or impaired patients.
How CORAT antibodies protect against severe COVID19
Recombinant human virus-neutralizing antibodies are the active component of the immunotherapy (also passive vaccine). Antibodies (immunogobulins, IgG) are molecules made by our own body to protect us against infections.
The CORAT antibody neutralize SARS-CoV2 after injection and immediately provides the protection in exactly the same way like antibodies would do from our own body once they are generated by the infection or by vaccination. The CORAT antibody stops the virus and protects the patients until their immunity generates their own antibodies. This drug should be very well tolerated, because it is identical to human antibodies (“fully human”). Due to the long serum half time, the CORAT antibody could be given in an early and acute stage of SARS-CoV2 infection with immediate antiviral effect and long protection until the body has the time to produce enough of its own IgG.
How are CORAT antibodies different from a typical vaccine?
A typical vaccine ("active vaccine”) consisting of dead or partial virus material cannot heal COVID19 patients. The reason is that active vaccines induce an immune response - typically the generation of antibodies (IgG) - like the infection does itself. However, the development of protecting antibodies takes up to 2-3 weeks, too long for patients with a severe infection to survive. Therefore, patients that are already infected do not benefit from such an active vaccine. The same is true for medical care personnel in emergency situations, because immunological protection starts only several weeks after the vaccination.
In contrast, CORAT antibody immunotherapy (also named "passive vaccine") supplements the not yet existing antibodies in the patient's body from the very time of injection, thus helping to lower the virus burden immediately. An active vaccine can protect healthy persons after some weeks, but it does not help patients already infected. Further, it cannot provide immediate protection to risk groups and exposed medical care personnel. CORAT antibodies can fill this treatment gap and thus perfectly complement virus-based vaccines.
As it will take many years to completely vaccinate the world's entire population, acute severe cases will be seen in our clinics for a long time to come, and a medication to help these patients is urgently needed.
Serum therapy is established since 120 years and well tolerated
Serum therapy uses (un-defined) mixtures of antibodies from immunized animals or convalescent patients to neutralize pathogens
Introduced by Emil v. Behring in the late 19th century (First Nobel prize for medicine 1901), countless children cured (diphtheria)
although effective, side effects of animal serum therapy were seen (which are completely avoided by fully human CORAT design)
IVIG (pooled human IgG from plasma donors) is still broadly used
ongoing clinical studies with human antibodies from reconvalescent donors are approved to treat COVID-19 (e.g. NCT04321421, NCT04292340 ). These blood derived products may show disadvantages, because they are mixed from many different donors (no defined drug) with different amounts of effective antibodies from batch to batch. In addition, there is also the potential risk of antibody enhancent.
Modern, recombinant neutralizing antibodies against intectious disease are approved
Synagis (Palivizumab), Prevention of RSV infection for children at risk
CORAT antibodies are made by Nobel-prize awarded molecular biology technique "antibody phage display" to isolate human monoclonal antibodies from blood that are indistinguishable from our own bodies antibodies - with one difference: they prevent SARS-CoV-2 infection
To minimize potential side effects, every biomolecule in a CORAT medication is made from a gene directy obtained from human donors, i.e. it has already been produced before in a healthy person - there are no synthetic parts, no chemical modifications etc. involved.
CORAT member TU Braunschweig has already successfully generated neutralising antibodies to other deadly viruses, for example our antibody X10H2 against SudanEbola Virus (protective in in vivo tests , PNAS. 2020 117:3768-3778 ), VEEV, WEEV, Marburg Virus, and many pathogenic Toxins.
Some of these antibodies, e.g. our antibodies against diphtheria toxins, performed better in inhibition than the currently used serum-derived clinical standard treatment, as confirmed by the NIBSC, see (Sci Rep. 2020, 10:571)
CORAT antibody prevents infection with SARSCoV2 isolated from COVID19 patient
Infection of cells (in cell culture) with SARS-CoV2 isolates from a COVID19 patient lead to their lysis, indicated by rounding and loss of confluence (upper left panel). Uninfected cells (upper right) grow normally (no dead round dots). Lower right: Adding the CORAT antibody from Yumab to infected cells completely protected the cells from infection for 5 days, while a negative control antibody (lower left panel) did not protect the cells (Fotos: light microscopy)
Originally initiated by Prof. Stefan Dübel, YUMAB founder and head of the Biotechnology Department of the University of Braunschweig and his colleague Prof. Michael Hust, together with Prof. Gundram Jung of University of Tübingen, CORAT expanded to a consortium of more than 30 scientists and clinicians from academic institutions and industry. CORAT members represent competence from infection research, antibody development and manufacturing to bedside and have joined forces to supply acute COVID19 patients with a well-tolerated treatment to eliminate SARS-CoV2.
Prof. Dr. Stefan Dübel Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics Spielmannstr. 7, 38106 Braunschweig, Germany Phone: +49-531-391-5731, Fax: +49-531-391-5763 email@example.com