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How many potential vaccines are currently under investigation?
As of May 11, 2020, the WHO lists 110 candidates for Sars-CoV-2 vaccines that are being investigated and tested by different pharmaceutical companies around the world. There are also approaches from universities that have never manufactured a vaccine themselves. Ten of these are already in phase I or II of the so-called clinical trial. That means: they are already being tested on humans.
What are the requirements for vaccine approval?
In order for the Paul Ehrlich Institute in Germany to approve a potential vaccine for a human clinical study, a manufacturer must first submit data that the substance has already been tested sufficiently preclinically, for example in animal experiments. Then the vaccine must be clinically tested in three phases:
Phase I: The vaccine is administered to a small group of healthy volunteers. It is observed if the agent reaches the target area in the body and there are no acute side effects.
Phase II: Only when phase I has been successful, the phase II vaccine can be administered to a larger number of participants who come from the risk group. In the case of Covid-19, it would be the elderly or people with previous illnesses. In this phase it is verified if the vaccine works, that is, it prevents the disease and what dose is appropriate.
Phase III: The vaccine can be tested in a representative group of volunteers: up to ten thousand test subjects are vaccinated. Phase III confirms the effectiveness, safety, and dose of the vaccine. Therefore, adverse events, such as a particularly severe course of the disease due to the administration of the vaccine, can be observed and excluded.
What approaches are in the clinical trial?
mRNA vaccines:
Two of the ten companies whose vaccine candidates are already in clinical trials, the German pharmaceutical company Biontech and the American company Moderna, are investigating so-called mRNA vaccines. Messenger RNAs are messengers in the human body that carry information about the protein model to the cellular machinery, where proteins are built.
In the case of a Sars-CoV-2 mRNA vaccine, blueprints for a virus coat protein are injected into the human body for production by the cells. As a result, the body recognizes them as strangers and produces, among other things, antibodies in a precisely tailored defense process. When in contact with the actual virus, the immune system can quickly activate this protection patrol and eliminate pathogens.
So far, not a single mRNA vaccine has been approved, and there is a lack of experience worldwide. “The fact that RNA vaccines have not yet been approved is not necessarily due to the fact that the technology is bad, but depends on several factors,” said the chairman of the Permanent Commission on Vaccination (Stiko), Thomas Mertens , in an interview with SPIEGEL. It is also a question of money, because research into new technologies has to be funded.
There is also a lack of tried and tested models for the mass production of mRNA vaccines. However, experts are confident that mRNAs could be produced relatively easily because they are not complex biomolecules.
Inactivated virus (killed vaccine)
Chinese companies Sinovac and Sinopharm are testing the safety and effectiveness of so-called dead vaccines at three institutes in the fight against Covid-19. Sars-CoV-2 viruses are isolated from infected viruses and spread in cell cultures that are approved for vaccine production. They are then chemically and physically inactivated so that they can no longer reproduce and be injected into humans. Inactivated viruses are recognized by the immune system as foreign and produce antibodies. Many important vaccines are based on this principle, for example against tetanus or hepatitis B.
Vector vaccines
Using genetic engineering, researchers can “disguise” harmless viruses as the new coronavirus. To do this, they exchange certain proteins on their surface for typical components of the pathogen. These so-called vector viruses pretend that the body is infected, but do not make it sick. The idea: those who are vaccinated with this type of vector virus form antibodies that also protect against a real infection. The first approved Ebola vaccine works like this.
However, vector vaccines are “genetically engineered regulatory drugs that are associated with considerable approval effort,” writes the “Science Media Center (SMC).” “Above all, the risk potential of the vector used must be explored.”
In the fight against Sars-CoV-2, the University of Oxford and the Chinese company Cansino Biological are already testing their candidate vaccines in humans in the first two clinical phases.
DNA vaccines
In another approach, which the American company Inovio is already investigating in humans, a section of DNA is introduced into human cells using a bacterial plasmid. This DNA sequence is said to stimulate the immune system to produce antibodies. However, this generally requires enhancers that can have undesirable side effects. “Until now, DNA vaccines have only been approved in veterinary medicine,” writes the SMC.
Why is this taking so long?
It has taken over a decade to prepare a new vaccine for the market. Because it will then be administered to healthy people, it must undergo particularly high security controls. Even under the highly optimistic assumption that one or more vaccine candidates will have successfully completed the approval process by the end of the year, there are likely to be problems in providing individuals with comprehensive coverage. Because vaccines have to be mass produced. However, there is no capacity for this.
Assuming that people would need two doses, almost eight billion doses of vaccine are needed if half the world’s population is to be vaccinated. Experts talk about the biggest challenges in the history of vaccine manufacturing. Giant companies like Sanofi can currently produce a billion doses a year, across all their vaccine pools. Other vaccines would have to continue to be manufactured, and bottlenecks have always been a problem throughout the industry, even with standard vaccines.
Who pays for the development of the vaccine?
The vaccine business has been dominated by four manufacturers for years: GlaxoSmithKline, Merck & Co., Pfizer, and Sanofi. Unlike pharmaceuticals, Europe is a leader in vaccine research; 80 percent of production also takes place in Europe. Many new suppliers are not expected because the barriers to entering the market are very high. The high investment costs to establish production facilities are responsible for this. The business with vaccines is profitable for the remaining suppliers: many have announced that they will increase their production capacities as much as possible.
The current problem is that preparations must be made for the preparation without knowing exactly which vaccine it will result in. Therefore, the pharmaceutical industry demands cost sharing and promises from politicians to guarantee certain purchase quantities.
Currently, vaccine development is also promoted through so-called product development associations; These are alliances that organize joint projects of foundations, government and aid organizations, research groups and companies. In this way, active ingredients can be developed that would not be economically viable for a single company. Germany participates in the CEPI project through the Federal Research Ministry.
And who will get the vaccine first?
To eradicate the virus, as many of the 7.8 billion people worldwide as possible would have to be vaccinated. With previous epidemics such as swine flu, the richest countries were always vaccinated for the first time, while the poorest countries were slow to receive their turn. This should be avoided this time, demand politicians, the World Health Organization and pharmaceutical experts. “First of all, fully vaccinating the population in one country and not in other countries, that is inconceivable in the sense of global solidarity,” said the head of the Paul Ehrlich Institute, Klaus Cichutek, in early May about SPIEGEL.
Criticism is a promise by French pharmaceutical manufacturer Sanofi to the United States government to grant special rights to the United States by ordering vaccines against the new coronavirus. Sanofi’s justification for the exception is that Americans were willing to take financial risks in vaccine development.
It could be conceived that there will be more geopolitical disputes: countries that have been heavily involved in financing may require that they have a prerogative of the first wave of vaccine deliveries. In any case, it can be expected that not everyone can be vaccinated immediately if a vaccine is available because the capacities will not be sufficient.
Pandemic plans stipulate that medical personnel and risk groups are vaccinated first. However, other systemically relevant professions, such as police officers or registrars (they must still be able to certify the death of people in the event of a pandemic) may also be among the first recipients.
Editor’s Note: In an earlier version, the first name of Klaus Cichutek, head of the Paul Ehrlich Institute, was incorrect. We have changed the passage.
