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“We’re talking about an uncertain period of time”

Medical scientist Hartmut Hengel explains why it takes so long to develop vaccines for the new coronavirus

Freiburg, Mar 27, 2020

Mid to end 2021. That’s when some experts believe an effective and safe vaccine for the new coronavirus SARS-CoV2 could be available in large quantities. However Prof. Dr. Hartmut Hengel, Medical Director of the Institute of Virology at Freiburg University Medical Center, is dubious: there is a lack of experience with the newer processes, development and safety assessments for the old ones take a long time.

Coronaviruses are a virus family with many members spread across several genera. The new coronavirus has come to light since the end of 2019 – and is more infectious than its relatives. Photo: photoguns/

How soon will there be a corona vaccine? “We’re talking about an uncertain period of time,” says Hartmut Hengel in response to high expectations: it is unlikely that there will be an approved vaccine in 2021 with a recommendation from the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute. Hengel knows what he’s talking about. For ten years he was a member of STIKO, now he is Deputy Chair of the Scientific Advisory Board of the Paul Ehrlich Institute, which is the Federal Institute for Vaccines and Biomedicines, and incumbent president of the German Society of Virology.

“We’ve already considered similar viruses,” Hengel explains. Originating in southern China, from November 2002 SARS or Severe Acute Respiratory Syndrome spread across almost every continent. By the official end of the pandemic in May 2004 over 8,000 people had fallen ill. Almost 800 people died – nearly 10 percent of those affected. The pathogen was named SARS-CoV1.

Its genome is almost eighty percent identical to the coronavirus SARS-CoV2 which is currently at large. “They’re brothers or at least closely related,” says Hengel. But the twenty percent genetic variation has consequences. “The pathogens have different effects on people.” You can see this simply in the figures on Covid-19, the disease caused by SARS-CoV2: by comparison this virus is more infectious. Covid-19 escalates faster, but claims a lower percentage of fatalities than SARS.

The spike protein is seen as the key to immunity

Likewise there are molecular differences. “The spike protein in both viruses is clearly different,” Hengel mentions as an important example. The spike is seen as the key to immunity. “It’s the primary antigen of coronavirus.” The active vaccine that we all long for would encourage the human immune system to produce antibodies against the spike and thus prevent infections. Coronaviruses attach to their host cells using the surface protein. Then the spike paves the way to the cell interior for the pathogens. However researchers in the state of Texas have observed that while highly-specific antibodies recognize the spike protein from SARS-CoV1, they don’t recognize the spike protein from SARS-CoV2. The latter has an enzyme interface, for instance, which its relative lacks, Hengel explains, “Details like this can make massive differences.” Researchers can’t learn much from vaccines that are supposed to counter coronavirus in animals. “Their effect wasn’t overwhelming anyway,” the expert laments.

Passive vaccination with antibodies

Differing strategies to develop vaccines also have different advantages and disadvantages. “In China they carried out isolated passive vaccinations for infections with SARS-CoV2, apparently also with a certain effect,” says Hengel. In passive vaccinations patients receive ready-made antibodies, for example from patients who have recovered. The advantage is that the antibodies provide immediate protection. However the protection ends rapidly because vaccinated patients degrade the injected antibodies and don’t produce them themselves. “Passive vaccinations are really only suitable in isolated cases.”

Active vaccinations – deactivated viruses or individual components

“Active vaccinations generate long-term immunity,” emphasizes Hengel. Some vaccines such as for mumps, measles and yellow fever contain reproducible but weakened viruses. “They’re still slightly virulent.” So people with severely weakened immune systems, for example after transplantations or during chemotherapy, must not be given such vaccinations. In addition it could be tricky to weaken SARS-CoV2 enough so that the virus no longer makes people ill but it still triggers an immune reaction that is neither too weak nor dangerously strong.

Excessive immune reactions can themselves cause severe side-effects. This risk exists with vaccines that rely on individual, isolated virus proteins plus adjuvants. Hengel recalls Pandemrix, a vaccine for the swine flu that was in circulation during 2009 and 2010. The substance led to cases of the severe disease narcolepsy – probably because of the adjuvant. “They can already cause problems in development. A lot of safety studies, even long-term, are necessary for such vaccines.” Some side-effects can be so rare that they cannot be picked up in clinical trials.

Active vaccinations with the “assembly instructions” – nucleic acids

With nucleic acids the bodies of those who are vaccinated can produce the virus proteins that their immune system has to respond to for themselves. The vaccines either contain only mRNA, a duplication of genes like those for the spike protein. Then these assembly instructions have to pass into the cells on their own. Other vaccines embed mRNAs in a vector – in the genome of another virus that carry the assembly instructions into the cells.

“The principle of the process with pure mRNA is safer,” says Hengel, “Without vectors, cells can’t incorporate mRNA in their own genome.” Because if that happens then new questions arise. Basically there is a lack of experience with the new methods: “So far there isn’t a single wide-ranging vaccination program.” Doctors have only used the process in a few severely-ill tumor patients, and therefore in completely different circumstances, the expert explains, “These vaccines aren’t suitable for the mass of cases yet, because no one precisely knows their risks.”

Oh, if only it were just a new flu!

Clinical studies involving several vaccines will probably take place until the end of 2021. Hengel does not however believe that any of them will complete all the clinical phases by then, be approved and able to be recommended by STIKO. Its recommendation guarantees a high level of protection with low risk. So the expert does not want to be drawn into forecasting when a safe vaccine for SARS-CoV2 could be available in large quantities. It would all be a lot easier if it were a new strain of flu virus. “We have very reliable vaccines for influenza viruses, which we can incorporate new antigens into. If things go well we’d have a new flu vaccine after three months.”

Jürgen Schickinger


Coronavirus: virus family with many members, spread across two subfamilies, several genera and subgenera.

SARS-CoV1: the pathogen of SARS, Severe Acute Respiratory Syndrome, which triggered a pandemic in 2002 and 2003.

SARS-CoV2: the pathogen of Covid-19, the acute respiratory disease that has spread to become a worldwide pandemic since December 2019.

Covid-19: name for the acute respiratory disease that is currently being caused worldwide by the SARS-CoV2 virus.