Scientists succeeded in developing vaccines against the new coronavirus that are clearly effective and safe in record time. How does the vaccine work? Do the vaccines deliver what they promise? And were they really carefully tested in such a short time?
Along with keeping your distance, quarantine and hygiene, vaccines are an important weapon in the arsenal against life-threatening infectious diseases. That's why intensive research is taking place around the world on developing vaccines against the new coronavirus SARS-CoV-2; the first vaccines have already been approved. The aim of the vaccine is to render large swathes of the population immune to the infectious illness. That means that they can't catch it from other people and will ideally not pass it on either. This could slow the spread of SARS-CoV-2 and prevent serious cases of illness.
Can the new vaccines curb the pandemic?
The announcements of over 90-percent effectiveness of the vaccines from BioNTech/Pfizer and Moderna sound confident. This could signal a turnaround in the pandemic. The Kiel-based virologist Professor Helmut Fickenscher has dampened expectations somewhat, however: "I am very curious as to whether the results of the phase III studies will be confirmed. I really hope so. But we can't yet predict how effective the vaccine will be in the population," said Professor Fickenscher, who heads the Institute of Infection Medicine. For Professor Regina Scherließ from the Institute of Pharmacy at Kiel University, it is still questionable whether the completely new vaccines will actually protect the particularly vulnerable at-risk groups. "These subgroups in the clinical trials need to be carefully evaluated."
Despite uncertainties regarding the extent and duration of its effectiveness, Professor Fickenscher is in favour of the vaccine. "The vaccine offers the opportunity to protect yourself and others against a serious infectious illness," said the infectious disease specialist. "We absolutely have to take this opportunity, especially considering the threat of long-term effects from Covid-19," added the pharmacist.
How does a vaccine work?
The aim of the vaccine is to train the body's immune system to recognise a germ or pathogen. Deadened, weakened, or even just parts of the pathogen (antigens) are administered which are no longer able to cause a serious illness. mRNA vaccines are a relatively new approach. This principle is used in the vaccines from BioNTech and Moderna. They contain genetic information from the pathogen which the body uses to generate a virus protein. The virus RNA is produced synthetically. "By contrast, in the classic approach to vaccine production, a protein is isolated from the virus and cleaned. That requires far more work," explained Regina Scherließ, who heads the Pharmaceutics and Biopharmaceutics working group.
Regardless of which procedure is used, the aim is always to simulate an infection in the body. It reacts to this by forming antibodies and what are known as memory cells. When these come into contact with real pathogens in the future, they quickly become active and can fight off the infection.
The clinical trials for the vaccines took place in record time. Were the risks and side effects really studied properly?
As with all trials for vaccines and medications, the tolerance and principal effectiveness are first studied in animals. Only after these preclinical trials is the vaccine tested on humans in three phases in clinical studies. Before the approval and use of a vaccine, its safety and effectiveness must be proven in different population groups, which means that all approved vaccines have completed all three phases. The bar for a vaccine is high, as it is intended for administration to healthy people. Even after it receives market approval, it is continuously monitored in order to detect rare problems.
In the clinical trials, the current successful vaccine candidates proved to be well tolerated. As is known from other vaccines, they can cause fever, headaches, tiredness, redness and pain at the injection site, and similar symptoms. This is a sign that the immune system is reacting to the vaccine. No severe side effects were observed. "The vaccines based on RNA are especially easy to produce. That's why development here is relatively fast," said Professor Fickenscher. He considers it extremely unlikely "that RNA vaccines have relevant side effects." This is because, according to the doctor of infection medicine, they do not use a complex antigen – so a weakened or deadened pathogen – but simply the blueprint for a virus protein. Aside from the newly approved corona vaccines, however, there have been no other approved vaccines to date that work on this principle, which means that there is as yet no experience of their broad application. Yet the principle isn't entirely new. Prospective vaccines and new types of cancer therapy have been developed on the basis of RNA for a long time.
One fear circulating on social media can certainly be quelled: "The mRNA administered with the vaccine is not built into the human genome because it has a different chemical structure. Instead, it is quickly inactivated and destroyed by the body's own enzymes," explained Professor Scherließ.
Why does vaccine development usually take so long or fail?
Various difficulties can arise when developing vaccines. "For example, scientists have long tried to develop a vaccine against the Ebola virus. It wasn't possible to test the prospective vaccines, however, because there were no outbreaks of the illness," explained the doctor of infection medicine, Professor Fickenscher. It wasn't possible to test the vaccine and prove its effectiveness until there was a major Ebola outbreak in West Africa. This vaccine was approved at the end of 2019. A functioning basic principle is key to development, said Helmut Fickenscher, "and where that isn't available, such as with the human immunodeficiency virus (HIV), hepatitis C virus or tuberculosis, things can take a very long time. When it is clear what happens, vaccine development is still complicated but can usually be completed within a few years."
How is the effectiveness of a vaccine measured?
While with a therapeutic substance, such as high blood pressure medication, tests determine whether the new drug lowers blood pressure more effectively than an ineffective dummy drug (placebo), a protective vaccine must prove that the infection does not occur. To do this, many people in a trial have to receive a vaccination with the new substance or with a placebo. And only once a certain number of infections have occurred can it be assessed whether fewer people fell ill in the vaccinated group than in the placebo group. "Within the clinical trials, we need to be sure that a certain percentage of test persons are actually exposed to the virus and either fall ill or do not fall ill," clarified Regina Scherließ. "That's why the studies took place in countries where the virus is widespread."
In the study by BioNTech/Pfizer, over 40,000 people were vaccinated. In the placebo group, 162 people contracted Covid-19 compared with 8 people in the vaccination group (N Engl J Med 2020; 383:2603-2615). This results in effectiveness of 95 percent. The phase-3 study data for the Moderna vaccine has also been published (N Engl J Med 2020 Dec 30). This reveals effectiveness of 94.1 percent for the Moderna vaccine, too. Yet Professor Fickenscher still considers these figures to be lacking for a precise indication of effectiveness. Reality will reveal just how effective the vaccine is. It is also unclear what kind of long-term effectiveness the vaccine brings. "A person can be infected with SARS-CoV-2 without showing any kind of sign of an immune reaction. And that's why we need to be open-minded about how well the vaccine really works and how often this phenomenon occurs," said Professor Fickenscher.
Author: Kerstin Nees
Explanatory video "How a vaccine is developed", Federal Ministry of Education and Research: