November, 2020
NIJZ

Due to the multiple negative effects of the COVID-19 epidemic, the development and testing of vaccines that could definitively slow down the spread of the disease is being accelerated.

A well-vaccinated population against COVID-19 would help to control the epidemic and relieve the burden on the health system and return life to normal, both in the private sphere and in economic activities.

The NIJZ has prepared an overview of vaccines and their development phases to help you better understand the meaning and action of vaccines, as well as to dispel the fake news and misconceptions circulating on social networks:

“Vaccination is usually used to introduce weakened or destroyed pathogens or their components (also called antigens) into the body to trigger an immune response. When we come into contact with a pathogen, our immune system recognises it and protects us from infection.

Vaccine development goes through well-defined pre-clinical and clinical phases. The pre-clinical phase involves identifying a suitable antigen that stimulates an immune response in the body similar to that of an actual infection. Cell culture and animal tests allow an assessment of the ability of the vaccine to elicit an immune response. These tests give researchers insight into the cellular responses that might be expected in humans, so that they can use the results to make an assessment of a safe starting dose for the next phase of research.

The pre-clinical phase of vaccine testing is followed by three clinical phases of testing:

  • Phase 1 involves testing on a small group of healthy adults (20-80 people). The main objective is to assess the immune response in vaccinated individuals and to adjust the amount of vaccine dose needed, as well as to assess the safety of the vaccine in the face of the occurrence of potential adverse reactions.
  • Phase 2 involves testing a larger group of several hundred participating individuals. Some of the individuals may belong to at-risk groups, in whom the disease may be more likely to cause a more severe course of disease. The aim of Phase 2 is to further study the safety and efficacy of the vaccine, to examine the proposed doses and to finalise the vaccination schedule and the route of administration. Phase 3 involves several thousand to tens of thousands of people. The aim of
  • Phase 3 is to assess the safety of the vaccines in a larger group of people in more detail, and to characterise the effectiveness of the vaccine (whether it prevents disease, also prevents infection, leads to antibody production, etc.) in more detail.


Following successful completion of Phase III clinical trials, manufacturers must obtain marketing authorisation from the competent authority for medicinal products (in Europe, the European Medicines Agency, EMA). Even after the vaccine has been manufactured and used in the population, regular testing and monitoring of the vaccine’s efficacy and safety continues in parallel.

The normal vaccine development pathway takes several years, but in the case of SARS-CoV-2 vaccines, it is much faster. Research teams have accelerated development by using data from past vaccine research (especially for SARS and MERS, which are related coronaviruses), by combining research phases and by using new vaccine development technologies. Despite the accelerated pace of vaccine development, vaccine safety needs to be thoroughly tested and ensured.

The main types of SARS-CoV-2 vaccines undergoing Phase III clinical trials are presented below.

Nucleic acid-based vaccines (mRNA)

These vaccines contain a piece of the SARS-CoV-2 genetic signature, which contains a transcript for a specific antigen (e.g. protein S, which the virus uses to bind to and enter human cells). This genetic signature is then used by the body cells to produce an antigen that elicits an immune response in the body. The advantage of this approach is the relative ease of large-scale vaccine production. A number of vaccines of this type are in the pipeline, but none is currently in widespread use.

DNA-based vaccines, which are currently still in the early stages of clinical trials, also belong to this group.

Researchers at the Slovenian Institute of Chemistry have also used an innovative method to develop their own vaccine, which is ready for clinical trials. The vaccine contains a piece of genetic code that is translated into viral proteins in human cells, which trigger antibody and cellular immunity. The novelty of the Slovenian approach is based on the modification of viral proteins into nanoparticles that resemble viruses, thus improving the immune system response.

Vector vaccines
Vaccines contain a virus (vector, e.g. adenovirus) that is harmless to humans and cannot cause disease. The gene for the SARS-CoV-2 antigen (e.g. protein S) is inserted into it. As a result, the vector produces the antigen, expresses it on its surface and thus triggers an immune response in the person.

Such vaccines have the advantage of stimulating the immune system well, resulting in stronger and longer-lasting protection. However, since the vector used to enter the cell is a virus, persons who have already developed protection against this virus may develop an immune response to the vector rather than to the pathogen antigen, which may reduce the effectiveness of the vaccine.

Inactivated (dead) vaccines

Inactivated vaccines contain a pathogen that has been previously inactivated (by heat or chemically). In this way, it loses the ability to reproduce and cannot cause infection. Inactivated vaccines elicit a weaker immune response than live attenuated vaccines and usually need booster doses to work sufficiently.

Vaccine from purified parts of the pathogen

Vaccines do not contain the whole pathogen, but only parts of it. This includes polysaccharide, conjugated, recombinant vaccines, toxoids, virus-like particles (VLPs). The SARS-CoV-2 purified vaccine, which is in phase III clinical trials, is produced using recombinant technology, where a piece of the genetic signature for the SARS-CoV-2 antigen (protein S) is introduced into cells (e.g. the SARS-CoV-2 antigen gene (e.g. the SARS-CoV-2 antigen gene). These cells then produce the antigen, which is well purified before use. The process ensures a high safety of the vaccine.

Other types of SARS-CoV-2 vaccines, such as live attenuated vaccines (described below), are also in development but have not yet reached phase III clinical trials.

Live attenuated vaccines

The vaccine contains an attenuated live virus that can replicate in the host but loses its ability to cause disease. This vaccine has the advantage of stimulating the immune system strongly and provides longer lasting protection than other types of vaccines after only one dose. This is because the vaccination induces an immune response that most closely resembles the actual infection. The downside is that the vaccine is not recommended for use in certain population groups, such as pregnant women and immunocompromised people.”

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EU Funds

The project is part-funded by the Ministry of Labour, Family, Social Affairs and Equal Opportunities and the European Union through the European Social Fund. The operation is financed under the Operational Programme for the Implementation of the European Cohesion Policy 2014-2020, Priority Axis 9 “Social inclusion and reducing the risk of poverty”, Priority Investment 9.1 “Active inclusion, including the promotion of equal opportunities and active participation, and improving employability”, Specific Objective 9.1.2 “Empowering target groups to move towards the labour market”.