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 at full speed on a vaccine against SARS-CoV-2. At the end of September, 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 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. The vaccine candidate has already been produced and filled there in large quantities.

Frequently asked questions | FAQs

„We are very glad that together with the DZIF we have succeeded in developing a vaccine candidate that is ready for the clinical test phases in such a short time.“
Dr Jürgen Betzing
CEO IDT-Biologika

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 first clinical trial started in early October after completion of the approval process. It 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

For more detailed questions, please contact the respective press office of the contact persons mentioned. If no contact person is specified, please send your questions to our DZIF Press Office.

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?

Financing of preliminary tests in a Phase I first-in-human clinical trial is assured. IDT Biologika GmbH has developed a cell line and a process for large-scale production of high-purity MVA vector vaccines. This platform technology was used to develop clinical test samples.

The MVA vector vaccine against SARS-CoV-2 has already been used to vaccinate mice, which have shown the necessary immune responses. Production of the vaccine for the first human clinical trials at the pharmaceutical company IDT Biologika has been completed. The vaccine has been prepared and further developed so that clinical trials can be conducted with this medication. Among other things, possible impurities were tested, the content of the active substance in the dosage form was determined exactly and the stability of the product was ensured.

At the end of September, the University Medical Centre Hamburg-Eppendorf (UKE) received approval from the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, and the Ethics Commission of the Hamburg Medical Association to start clinical trials. For this purpose, in addition to the data on the quality and production of the vaccine and the preclinical and clinical data, the so-called study protocol - the document containing detailed information on the course of the study, the study participants to be included, the participant information, as well as the relevance and objective of the study - was also reviewed. The authority has examined the documents primarily with regard to the quality, efficacy and safety of the vaccine and according to scientific and technical aspects. The focus of the Ethics Commission was on whether the study is justified and feasible, whether sufficient preclinical data are available and whether the rights and safety of the study participants are ensured, and in the examination whether the study center and the investigators are qualified. With the rather complex regulatory and bureaucratic process, a high level of safety of the study participants as well as a high study quality can be guaranteed.

Phase I clinical trials started in October 2020. It is being conducted at the UKE Hamburg-Eppendorf in cooperation with the Clinical Trial Center North (CTC North). On October 9, the first volunteer was injected with the vaccine MVA-SARS-2-S against COVID-19. The readiness to participate in COVID-19 vaccine studies is very high.

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, scheduled to begin in October, a total of 30 healthy volunteers will initially be vaccinated. In the first phase, volunteers aged 18 to 55 years will be included. For safety reasons, older people will only be included in the second phase (II). 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 this year; it will include further groups of subjects, including older people. 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 600 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?

Persons over 18 years of age can register for participation in the clinical trials at the following e-mail addresses:

info-covid@uke.de or

info@ctc-north.com

When will the DZIF vector vaccine be available?

We expect that a ready-made vaccine will be available for an accelerated approval process by the end of 2021. Even though this is only a year and a half from detection of the virus to approval of a vaccine - an absolute record in this field - our high scientific and ethical standards also apply to our SARS-CoV-2 vaccines.

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

The immunological reaction of the body is very similar to that with a natural virus infection. It is not possible to predict 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

Who are the partners in this project?

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

How is this vaccine project funded at the DZIF?

Vaccine development entails expenses in the tens of millions. For SARS-CoV-2 vaccines, there is also a risk because vaccines must be developed very quickly without compromising the efficacy and safety of the vaccines. This can only be ensured by many parallel investigations, which would normally be carried out one after the other. This also increases the financial risk for these developments. However, it is expected that the vaccine will be made available in large quantities at low prices, in order to avoid overloading the health system even further. These objectives can only be achieved with an appropriate funding programme. A special programme of the Federal Ministry of Education and Research will help to accelerate the research and development of urgently needed vaccines against SARS-CoV-2. IDT Biologika GmbH is providing further funding for the development. IDT and DZIF will apply jointly for funding. They are also prepared to work with other partners in order to speed up financing and implementation of the project.

What are the biggest hurdles in the development of the MVA vaccine at the moment, and how confident are you that it will work?

Until now, the greatest hurdles to large-scale production of MVA vector vaccines have been the availability of efficient cell lines and scalable technologies. Furthermore, the purity of vaccines has always been a challenge. These challenges have been solved with IDT’s technology platform. The stability of the MVA vectors was rarely assured. This problem has also been solved by the excellent experience of the DZIF, in particular the LMU. IDT’s cell technology and the LMU’s MVA vector are very well tolerated. This is vital for a safe and effective vaccine.

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

email to the Press Office of the LMU Munich

About 200 vaccine projects dealing with the new SARS-CoV-2 coronavirus are underway worldwide. The DZIF is responsible for two vaccine projects, but is not ahead of the race. Is the DZIF vaccine coming too late?

In this situation, it is not crucial to be the first. In the end, it is likely that there will be more than one vaccine, and we will also need several vaccines for different target groups: Live vaccines, including the vector vaccine, can only be used to a limited extent in patients with a reduced immune response. MVA vector vaccines cannot be propagated, and it has been shown that the vaccine is effective and safe even in immunologically impaired patients. This is an advantage of the MVA concept.

However, inactivated vaccines can also be used, i.e. vaccines that can no longer spread in the body. It is also possible that different vaccines are suitable for different age groups. This will be clear from the initial results of clinical trials, which will be available from the second half of 2020.

The DZIF regards it as vital that we end up with a safe product. Although it may feel as though the vaccine should have been ready months ago, development of vaccines has never been as fast as that of SARS-CoV-2.

How can we ensure that even poorer countries receive enough of the vaccine?

The authorities, many international organisations and other stakeholders are involved in the debate on vaccine distribution. Scientists, doctors, donors and politicians from over 30 countries and over 70 institutions have formed an international coalition to respond to COVID-19 in developing and emerging countries. This association (the COVID-19 Clinical Research Coalition) aims to accelerate much-needed COVID-19 research in the world's resource-poor regions. In Africa, Latin America, and certain Eastern European and Asian countries, the virus could have a devastating effect on overloaded health systems. The German Center for infection Research (DZIF) was the first organisation in Germany to join the coalition.

IDT is working closely with the CEPI to provide resources and technologies for the production of SARS-CoV-2 vaccines to support global vaccine delivery.

Contact person for in-depth press enquiries: Prof. Jürgen May

email to the Press Office of the BNITM

Can the knowledge and experience of the DZIF be used in future epidemics?

The platform developed for the SARS-CoV-2 vaccine is already building on the platform for the MERS vaccine, and will make adaptation and development of vaccines faster in future epidemics.