Corona vaccine development at the DZIF

Vaccine development and testing at DZIF is carried out with the greatest care.

© DZIF/Science in HD

Scientists at the German Center for Infection Research (DZIF) are working on a vaccine against SARS-CoV-2. The special characteristic of this vaccine is, that the genetic information for a surface protein of SARS-CoV-2 is inserted into a modified and thus harmless Modified Vaccinia Virus Ankara (MVA). The MVA vector has been researched for many years and has been successfully used in other vaccine projects. For this vaccine development, the DZIF works together with the company IDT-Biologika in Dessau.
At the end of September 2020, the University Medical Centre Hamburg-Eppendorf (UKE) received approval from the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedical Drugs, and the Ethics Commission of the Hamburg Medical Association to start clinical trials. On October 9, the first subject was injected with the vaccine MVA-SARS-2-S against COVID-19. The results were available in January 2021: The vaccine proved to be safe, but the effect fell short of expectations. After a thorough investigation of the causes, the phase I trial has been continued with an optimised vaccine since July 2021.

Background

Since the new coronavirus SARS-CoV-2 first appeared in China, the scientists and physicians at DZIF have been accompanying the development with their research work. Under the direction of Prof. Gerd Sutter, virologist at the LMU Munich, a so-called vector vaccine is being developed, based on the "Modified Vaccinia Virus Ankara" (MVA) as a vector. MVA was developed at the LMU as a vaccine against smallpox over 30 years ago. MVA viruses are attenuated in such a way that they can be used as harmless vectors in other vaccines. They are not capable of reproduction, but the introduced gene information feigns an infection to the immune system and stimulates the production of antibodies and cellular immunity. This vector has already been successfully used at DZIF for the development of a vaccine against the MERS coronavirus, a close relative of SARS-CoV-2.

Development

DZIF scientists at the LMU Munich, the Phillips-Universität in Marburg and the UKE Hamburg were able to start the development of a new vaccine against SARS-CoV-2 quickly after the outbreak of the corona epidemic, as they had the necessary basic knowledge with the development of a MERS vaccine. At the LMU Munich, Gerd Sutter's team created a stable MVA virus with a component of the corona virus. The company IDT-Biologika developed a cell line and a process that is the only way to produce a highly pure MVA vector vaccine on an industrial scale. The first vaccine doses were filled in July. The clinical is headed by Prof. Marylyn Addo (UKE Hamburg-Eppendorf) and conducted at the Clinical Trial Center North. In Marburg, Prof. Stephan Becker's team will carry out immune monitoring - i.e. the characterisation of the antibody response to the vaccine.

Partners

  • LMU Munich (Gerd Sutter)
  • Phillips-Universität in Marburg (Stephan Becker)
  • UKE (Marylyn Addo) und CTC North (Saskia Borregaard)
  • Medical Center of the LMU Munich (Michael Hölscher)
  • University Hospital Tübingen (Peter Kremsner)
  • IDT Biologika (Andreas Neubert)

FAQs - Frequently asked questions

What is a vector vaccine and which vector is used in the DZIF?

Vector vaccines are genetically modified (and therefore harmless) viruses that serve as vectors for inserting the genetic material of a pathogen into target cells – in this case SARS-CoV-2. The viral vector cannot multiply by itself, but the DNA sequence that is introduced – the component of the coronavirus – can imitate an infection and trigger the production of antibodies.

Under the direction of Prof. Gerd Sutter, who is a virologist at the LMU university in Munich, a vector vaccine based on the "Modified Vaccinia Ankara" virus (MVA) is being developed in the DZIF as a vector. This MVA virus was generated at the LMU as a vaccine against smallpox more than 30 years ago. This vector has already been used successfully at the DZIF for development of a vaccine against the MERS coronavirus. The components of the virus against which the human body is hoped to form antibodies are necessary for the effect of the vaccine. The scientists selected the spike protein on the surface of the SARS-CoV-2 virus as the appropriate coronavirus component. This protein helps the virus to enter human cells. The corresponding gene sequence, i.e. the genetic blueprint of this protein, is then combined with the genetic information of the MVA vector. The genetic information for the surface protein of SARS-CoV-2 is incorporated into the MVA platform. The resulting vaccine virus then penetrates the cells as due to the vaccination and synthesises the spike protein, which is recognised by the immune system as "foreign" and thus stimulates the immune response. Specific antibodies and T-cells are formed against the spike protein, which should prevent later infection by the virus.

Contact person for in-depth press enquiries: Prof. Gerd Sutter

email to LMU's (Office of Communications & Media Relations

What is the current state of development of the SARS-CoV-2 vaccine?

Phase I clinical trials were conducted at UKE Hamburg-Eppendorf in cooperation with the Clinical Trial Center North (CTC North). Initial data analysis showed good tolerability, but immune responses were below expectations. The start of the second phase of the study was therefore initially suspended in early 2021. Since July 2021, clinical testing has continued with an optimized vector vaccine.

Now 30 volunteers are being sought to test the dosage of the vaccine, its tolerability and the immune response. A database of subjects has already been started at UKE and CTC North.

Contact person for in-depth press enquiries: Prof. Marylyn Addo

email to the Press Office of the UKE Hamburg-Eppendorf

What happens during the clinical trials of phases I, II and III?

Phase I Clinical Trial: Safety Test

In the Phase I clinical trial, a total of 30 healthy volunteers are vaccinated. In the first phase, volunteers aged 18 to 64 years are included. The vaccination is performed as an injection into muscles of the non-dominant upper arm. Subjects are then monitored for a few hours at the Clinical Trial Center North, an institute specialised in early phase studies on the UKE site in Hamburg, and then discharged home. During the following six months, the subjects are examined regularly, the injection site is examined, blood is taken and the tolerability is documented with a questionnaire. Side effects such as fever, headache, muscle pain etc. are recorded in a study diary. In addition to safety, the immune response (formation of antibodies and T-cells) of the body is measured and compared with the desired immune response, which COVID patients also show.

Phases II and III

If the results are positive and safe, the Phase II study will be launched; it will include further groups of subjects. In addition to Hamburg, Tübingen, Munich and other study centres will also be involved in these Phase II trials. In the Phase II clinical trial, the vaccine will be tested on approximately 700 volunteers. In this phase it is important, among other things, to find the right dosage and to test the safety and efficacy again and again.

Phase III is decisive - about 14,000 test persons are to be included here. The concept for Phases II and III trials is currently being further developed, but it also depends on the course of the pandemic. Trials are also planned in Africa, where the DZIF has close partnerships.

Who can take part as a subject in the clinical trials, and how can I apply?

An optimised DZIF vector vaccine is being tested from July 2021. Healthy volunteers between the ages of 18 and 64 who have not yet been vaccinated against SARS-CoV-2 nor have contracted SARS-CoV-2 in the past are still being sought for the study:
The study includes a health screening, two vaccination appointments and 14 control appointments within a period of seven months. The volunteers will receive an expense allowance. Those interested in participating in the study can contact the medical contracting institute CTC North:

email
Phone: +49 40 524719  111

Interested in participating?

What is known about the efficacy of the DZIF vaccine, and how long is it expected to work?

Nothing conclusive can yet be said about the immunological reaction in the body and the sustainability of the vaccine's effect.The immune response found in the trials may provide some evidence. In order to confirm the effectiveness of a vaccine, one has to demonstrate the protective effect of the vaccine against an infection or disease. This often requires vaccination of a large number of people who could be exposed to the pathogen.

Contact person for in-depth press enquiries: Prof. Stephan Becker

email to the Press Office of the Phillips-Universität in Marburg

Where and how are the vector vaccines produced?

After development in the laboratory, in which the desired DNA sequence is cloned into the genome of the viruses, IDT Biologika takes over production of the vaccine on a larger scale. IDT has nearly 100 years of experience as a vaccine specialist, with outstanding competence with development and approval of viral and bacterial vaccines. Together with the DZIF, IDT recently developed a method for producing a vaccine against another coronavirus (the MERS virus) that was funded by the Coalition for Epidemic Preparedness Innovations (CEPI). CEPI has contributed significantly to the development of the technologies now available. Together with the DZIF, IDT is now applying this knowledge to production of a vaccine against SARS-CoV-2.

Contact person for in-depth press enquiries: Dr. Andreas Neubert

email to the Press Office IDT Biologika