Vaccines are one of the greatest achievements in medicine. Developing vaccines is expensive and time-consuming, and a large number of early-stage products never reach the finish line.
Vaccine development will only begin when there is a clear need for the vaccine and when it is certain that the vaccine will also be used if it can be developed.
“To develop a vaccine, you first need to know the pathogen, how it causes disease, and how the disease progresses. The structure of the pathogen must be known and its components suitable for a vaccine must be identified. If entire microbes are used, they must first be weakened or inactivated. When only parts of a microbe are used, an immune boosting component is often added,” says Anu Kantele, Professor of Infectious Diseases at MeVac, the Meilahti Vaccine Research Center of Helsinki University Hospital.
“Vaccine research is based on and applies basic medical research. It provides insight into pathogens and the mechanisms and structures central to how the pathogen causes disease and helps to identify the components that produce an adequate immune response to the disease,” Kantele explains.
First, laboratory tests
A lot of basic research has been done before vaccine development can begin. It gives you an idea of what the vaccine could be like.
“A vaccine is first tested in a laboratory. Its safety and adverse effects, how it stimulates the immune system and its potential protection are assessed by animal testing. A manufacturing process that meets strict criteria will be developed for a promising vaccine. This is a preclinical phase, known as Phase 0,” Kantele says.
A four-phase testing process in humans
The next step is the clinical stage where the vaccine is tested in the human body. It consists of four phases.
In Phase I, the vaccine preparation is administered to a human for the first time. The tests are small-scale (typically 20–100 volunteers) and ensure that the vaccine is safe for humans, seeking the best dose and measuring the immune response to the vaccine.
Phase II clinical trials are more extensive (typically 100–999 volunteers) and are performed, at least in part, on the target population for which the vaccine is designed. The safety, side effects and immune response of the vaccine are further investigated and the efficacy of the vaccine is measured. The volunteers are divided into two groups, one receiving the test vaccine and the other receiving either a placebo or a known vaccine already in use.
Only very few vaccines reach Phase III. They are studied in a larger group of people, typically thousands of volunteers. Subjects are divided into two groups in the same way as in Phase II. If the vaccine proves safe and effective, the manufacturer can apply for a marketing authorisation for the vaccine.
In Phase IV, the vaccine has already been authorised and has become widely used. At this stage, rare adverse reactions are recorded and long-term efficacy is measured. In Finland, monitoring is largely based on registers. This is a statutory safety oversight and it is conducted by the Finnish Institute for Health and Welfare (THL) and vaccine companies, among others.
“Clinical vaccine development is highly regulated and adheres to strict ethical principles,” says Kantele.
Challenging and expensive development
“Vaccines are developed in broad international collaboration involving several countries. Basic research can often be academic research supported by many different bodies and organisations. Clinical testing of vaccines in a large human population is enormously expensive and therefore usually cannot be done with public funds. In practice, this is often done by vaccine companies,” says Kantele.
Research and development of vaccines is resource intensive and the development of a single vaccine can cost hundreds of millions of euros. Because of all the challenges involved in the development process, vaccine development work can easily prove to be economically unviable.
When will there be a vaccine against the coronavirus?
Under normal circumstances, it takes 10–25 years to develop a vaccine. In exceptional circumstances, compromises have to be made with the requirements of normal vaccine development, but work is still slow as certain steps cannot be bypassed.
“The WHO Director-General has estimated that development period for a coronavirus vaccine will be 18 months. It is a very tight schedule because there is a huge amount of work involved in each step of the development process. In addition to China, a vaccine is being developed in at least Australia, the United States and the UK,” Kantele says.
The WHO has provided detailed guidance on the conditions that must be fulfilled before a vaccine can be made available for wide use. This accelerates vaccine development, which is carried out as openly as possible in cooperation between pharmaceutical authorities and researchers. For example, the coronavirus genome was immediately made available to everyone.
Vaccine research in Finland
In addition to MeVac, THL and the Vaccine Research Center of Tampere University conduct vaccine research in Finland. Research may be specific to a research institution or ordered by vaccine companies. For example, different parties can collaborate by recruiting subjects for the same research.
“Finns readily take part in vaccine testing. We have very strong trust in healthcare and vaccines. Finnish volunteers are also exceptionally good and reliable subjects, who often do their best to play their part well in research. Hats off to Finns!
Anu Kantele, Professor of Infectious Diseases at MeVac,
the Meilahti Vaccine Research Center of Helsinki University Hospital.