The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, monitors the quality, safety, and efficacy of vaccines. The COVID-19 pandemic has brought the various types of viral vaccines against respiratory diseases into the focus of public interest. The Paul-Ehrlich-Institut explains the most common forms of vaccines in the following text.
Vaccines are preventive medicines that use the acquired immune system for targeted protection against infectious diseases. Vaccination trains the humoral (antibody-based) and cellular (cell-based) immune systems to successfully fight pathogens. Vaccines use pathogens to simulate an infection in the body. This process of active immunisation trains the immune system to combat viral infections. When a vaccinated person comes into contact with the pathogen, the defence system is already equipped and can react quickly. Thanks to vaccination protection and pathogen-specific immunity, an illness either does not occur at all or has a milder course. Sufficient vaccination protection often needs to be built up by administering more than one dose of vaccine. Many vaccinations wear off over time, but can be extended by booster vaccinations if necessary.
The principle of vaccines is to present virus components to the immune system in order to generate an immune response that is specifically directed against the virus. These virus components are called antigens. The virus vaccine classifications help to differentiate between the various types. Dividing virus vaccines into two groups, live vaccines and various forms of dead vaccines, was a tried and tested approach in the past. After the development of genetic vaccines, differentiation into three groups became the standard:
Live virus vaccines contain an attenuated (weakened) form of the virus that is capable of reproducing for a limited period of time, but can no longer cause the infectious disease associated with the wild-type virus. An example of this type of vaccine is the live-attenuated influenza vaccine, which is authorised for children and adolescents and is delivered via intranasal administration.
Inactivated virus vaccines, also called dead vaccines, contain either the entire virus in inactivated form or individual virus components. They are often combined with an adjuvant to stimulate not only the humoral but also the cellular immune response.
Whole virus vaccines contain the entire virus in inactivated form, often in combination with an adjuvant.
To produce the vaccines known as split vaccines, viruses are broken up with the help of solvents and the remaining fragments are purified. A more comprehensive purification of individual viral components is used in the production of subunit vaccines. In this process, the surface of the viruses is completely dissolved and the desired proteins are extracted in a targeted manner via purification. Both methods are used for flu vaccines, meaning that there are split and subunit vaccines against seasonal flu.
Proteins for vaccines can also be made using biotechnological methods in cell cultures (in yeast cells, for example). This is the process for producing recombinant protein vaccines. An example of a recombinant protein vaccine is the hepatitis B vaccine.
Certain viral proteins can join together into virus-like particles (VLPs), which enhances the immune response. VLPs are not capable of reproduction. An example of a VLP vaccine is the HPV (human papillomavirus) vaccine.
Genetic vaccines operate via the transfer of nucleic acids (DNA or RNA). The nucleic acids are applied in vivo, meaning within the body. They are either packaged in lipid particles or are part of the genetic material of virus particles that act as gene shuttles. The transferred nucleic acids contain the blueprint for the antigen, which is produced by the host body cells and presented to the immune system.
mRNA vaccines are an example of a gene-based vaccine. They are currently playing an important role in combating the COVID 19 pandemic. A large number of RNA and DNA vaccine doses can be produced in a short time.
In mRNA vaccines, the genetic information for a viral protein is contained in the form of ribonucleic acid (RNA). RNA performs various functions in somatic cells, including acting as messenger RNA (mRNA). With the help of mRNA, the genetic information in the genome of somatic cells is transmitted (via its messenger function) to the protein production machinery in the cell. The blueprint stored in the mRNA is used by the cell to produce the corresponding protein; in the case of the mRNA vaccines, this is a viral protein. Cell-free RNA is very unstable. It is therefore packaged in small fat particles to achieve better stability and enable efficient uptake into the cell. mRNA is only present in somatic cells for a limited period of time and is then eliminated.
DNA vaccines contain deoxyribonucleic acid (DNA). DNA vaccines include the genetic information of a viral protein and information for the machinery present in cells so that it can form mRNA containing the blueprint of the viral protein. The blueprint stored in the mRNA is used by the cell to produce the corresponding protein. DNA is significantly more stable than RNA. Similarly to RNA, DNA is packaged in small fat particles to enable efficient uptake into a small number of somatic cells. DNA is also only held in somatic cells for a limited period of time and is later eliminated. DNA vaccines have already been authorised for use in animals. DNA vaccines for use in humans are being developed against diseases such as COVID-19.
Like mRNA and DNA vaccines, vector vaccines also contain the genetic information for a viral protein (antigen). Here, however, the genetic information is incorporated into the genetic material of vector viruses that serve as gene shuttles or as attenuated hybrid viruses capable of reproduction. Vector viruses can be known vaccine viruses such as the measles virus (live attenuated vector vaccine) or attenuated, harmless cold viruses (adenovirus vector-based vaccines). The vector viruses are modified in such a way that they do not cause disease in humans. By transferring the genetic information contained in the vector vaccines to body cells, a viral protein is produced just like in the mRNA or DNA vaccines, which triggers an immune response.
The first mRNA vaccines in the world to be authorised by a drug regulatory agency were BioNTech/Pfizer's Comirnaty and Moderna's Spikevax COVID-19 vaccines. mRNA technology had been the subject of intensive research for many years before the development of the COVID-19 vaccines, e.g. in the context of the development of novel RNA-based cancer immunotherapies.
The COVID-19 vaccines Vaxzevria (AstraZeneca) and COVID-19 Vaccine Janssen are adenovirus vector-based vaccines. Both vaccine concepts – the mRNA vaccines Comirnaty and Spikevax as well as the vector vaccines Vaxzevria and COVID-19 Vaccine Janssen – contain genetic information for the spike protein. SARS-CoV-2 uses the spike protein to attach to somatic cells and infect them. Neutralising antibodies produced after COVID-19 vaccination bind to the spike protein in the event of a SARS coronavirus-2 transmission, preventing or reducing infection of cells.
Nuvaxovid, from the company Novavax, is a recombinant protein vaccine that belongs to the VLP vaccine group, since many individual molecules of the recombinant spike proteins stored in the vaccine as antigens cluster together to form virus-like particles (VLPs). The aggregation of the proteins into VLPs leads to an improved immune response.
The Paul-Ehrlich-Institut provides reliable and scientifically correct information on the authorisation, safety, and efficacy of vaccines to the public. The Institute's website provides information on all vaccines authorised in Germany. All information on the COVID-19 pandemic that has been published on the website of the Paul-Ehrlich-Institut to date is compiled in the coronavirus dossier.
The World Health Organization (WHO) provides information on its website about all COVID-19 vaccine candidates currently being tested in clinical trials worldwide.
Updated: 21.02.2022
