March 23, 2020
“Fast-track scenarios are being considered.”
We interviewed virologist Dr. Sebastian Ulbert, head of the department of immunology and its vaccine technologies unit at the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig, about the current status of research into a vaccine against COVID-19.
Dr. Ulbert, how long does it take on average to develop a new vaccine or antiviral drug?
In the case of vaccines, we are looking at a process that takes between five and ten years. The development of antiviral and other drugs sometimes requires less time. The determining factor is the scope of the clinical trials necessary to obtain approval of the new drug.
What does this involve?
Drug development basically consists of a preclinical and a clinical stage. The preclinical – or research and development – stage can sometimes be relatively short; for instance, when the task is to adapt an existing, already approved vaccine to a related pathogen, as in the case of seasonal flu vaccines. But in the case of pathogens for which an approved vaccine doesn’t exist yet – like the coronavirus – this stage can stretch over several years.
How do you know if a drug or vaccine is effective?
The drug or vaccine candidates are first tested on laboratory animals to establish their safety and efficacy. Clinical trials on humans, where costs can run to millions of euros, are not started until animal testing has produced good results. This stage of the process consists of several phases, the first of which is devoted to testing for side-effects on small groups of 10 to 20 healthy subjects. In the subsequent phases, the focus shifts toward proving efficacy. Clinical trials of vaccines are far more challenging than those for other drugs, because you can’t just concentrate on patients with the disease. On the contrary, vaccines are designed to prevent people from contracting the disease in the first place. So, in order to conduct these clinical trials, large cohorts of volunteers who are potentially at risk of an infection must be vaccinated. The number of test subjects can quickly escalate into the thousands. And it usually takes several years to gather enough statistical data – by comparing these results with those of non-vaccinated control groups – to determine whether the vaccine is effective or not. Approval is only granted if the results clearly prove a positive effect.
Can this process be accelerated in acute emergencies, such as the present one?
Obviously, this process is much too slow to cope with rapidly spreading pandemics. In the wake of the Ebola and Zika virus outbreaks a few years ago, the WHO started discussing with drug approval agencies the possibility of fast-track scenarios to speed up the clinical development of vaccines. In extreme cases, it may even be possible to omit large-scale efficacy studies with humans altogether. But only on condition that the vaccine is well tolerated and triggers an immune response in humans that correlates with the results of the preclinical animal tests – for example, by stimulating the production of disease-specific antibodies. The current coronavirus pandemic adds a sense of urgency to this debate.
What approaches are being considered?
At present, there is no vaccine to combat the SARS-CoV-2 coronavirus. But numerous companies and research laboratories are working day and night to find a solution. Some promising approaches developed during previous outbreaks of coronavirus (SARS, MERS) may now be adapted to the new virus. Another much-discussed option is the use of new technology platforms to deliver the vaccine antigen in the form of messenger RNA. However, this is a controversial issue among experts, with some doubtful that this method is suitable for mass production of vaccines. For one thing it is expensive; and, as yet, there is very little data as to whether it could lead to a robust immune response in humans exposed to the pathogen.
What contribution can Fraunhofer IZI make to this research?
Fraunhofer IZI possesses the virology expertise and the necessary infrastructure – our S3 laboratory – to work with SARS-CoV-2 and related viruses. We have already received requests from university and industrial research laboratories to test active drug ingredients for combating SARS-CoV-2 infections, and to provide supplies of virus material. We are currently setting up these projects. Another aspect of our research concerns the inactivation of viruses and other pathogens. We have formed a consortium with Fraunhofer FEP and IPA to establish low-energy electron radiation as a method in vaccine production, and we recently licensed this process to a major pharmaceutical company. Exposure to low-energy electron radiation is also a quick and effective way of inactivating the viral load in infectious patient material. And, last but not least, this work is supported by our expertise in the diagnosis of viral infections. Several of the technologies developed by Fraunhofer IZI for specific test systems can be found in diagnostic products already available on the market. These are now being adapted to the new strain of coronavirus.