Influenza viruses continuously change the surface proteins to which the human immune system responds, a process known as drift. In order to ensure protection against influenza, manufacturers adapt the influenza vaccines every year to match the virus strains and virus variants that are expected to circulate.
Flu vaccines are first given an initial marketing authorisation. The marketing authorisation holder must then obtain an authorisation for the seasonal strain update from the competent authority in order for their vaccine to be placed on the market in Germany and the European Economic Area (EEA) during the flu season. Depending on the vaccine product's intial authorisation procedure, different responsibilities arise for the subsequent strain update authorisation:
The list of seasonal influenza vaccines authorised in Germany on the Paul-Ehrlich-Institut's website indicates whether a strain update has been approved by including the adaptation year in the name of the vaccine product. If an influenza vaccine product is included in the Paul-Ehrlich-Institut's vaccine list but their name does not include the current year, this indicates that the vaccine has been authorised but no seasonal strain update has been carried out. These influenza vaccine products are not allowed to be placed on the market or used in the current influenza season.
Seasonal influenza vaccines are adapted annually to the virus variants expected to be in circulation (known as the strain update). It is important that the virus components (antigens) contained in the vaccine are as close a match as possible to the virus strains and virus variants that are expected to circulate in the coming influenza season. This approach ensures the best possible immune protection.
The World Health Organization (WHO) continuously obtains data on the circulating influenza strains via the GISRS network (Global Influenza Surveillance and Response System). Based on this information, WHO updates its annual recommendations for flu vaccine composition for both the northern and southern hemispheres.
The influenza vaccine products approved for a given influenza season in Germany and the EU contain the antigens of the variants of certain influenza virus strains expected in Europe, as recommended by WHO and the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA).
The Measles Protection Act (Masernschutzgesetz) has been applicable since 1 March 2020. The aim of the "Act governing the protection from the measles and the reinforcement of infection prevention by vaccination" (Gesetz für den Schutz vor Masern und zur Stärkung der Impfprävention) is to provide a better protection from measles infections, especially for children. More detailed information on vaccinations against the measles have been elaborated jointly by the Federal Ministry of Health, the Federal Office for Health Information (Bundeszentrale für gesundheitliche Aufklärung, BzgA), the Robert Koch-Institut and the Paul-Ehrlich-Institut. This information also contains answers with regards to the composition of vaccinations, the question of why a multiple component vaccine should be used, etc.
Since viruses require a live cell to replicate, a cell line (cell culture) from animals or humans is required to produce vaccine viruses. Depending on the virus type, various cell types or cell lines have proved to be particularly suitable for this purpose. For influenza vaccines, for instance, up to now, these have been primarily embryonised hen’s eggs; measles viruses and mumps viruses are replicated on chicken fibroblasts, rubella viruses and chicken pox viruses on human diploid cells (MRC-5).
There are currently two cell lines from human lung tissue for the production of marketable vaccines in Germany. In 1961, the scientist L. Hayflick developed the cell line WI-38, and in 1966, the scientist J. P. Jacobs developed the cell line MRC-5 (Medical Research Council). These cell lines are described as human diploid cells (HDC).
With the development and authorisation of vector vaccines to prevent COVID-19 disease caused by the SARS-CoV-2 virus, two additional cell lines have been added.
These vector vaccines require an attenuated virus as a means of transport (vector) for a harmless portion of the genetic information of SARS-CoV-2 into a small number of somatic cells. AstraZeneca's Vaxzevria and Johnson&Johnson's COVID-19 Vaccine Janssen use adenoviruses for this purpose.
In the case of Vaxzevria, these viruses are propagated on the cell line 293 HEK (Human Embryonic Kidney), in the case of Johnson&Johnson's vaccine on the cell line PER.C6 (from human fetal retinal cells).
The cell line 293 HEK was developed in 1973 by Frank. L. Graham, a doctoral student of Alex J. van der Eb.
The PER-C6 cell line was generated in 1998 by Frits J. Fallaux, also in the laboratory of van der Eb, by an immortalisation of embryonic retinal cells. These came from a fetus aborted in 1985.
The term "cell line" means that this line has been created as a unique line, and has since then been replicated and frozen. The cells are cultured. No new foetuses are required, as can be frequently read. No foetus was aborted in any case to serve as starting material for the establishment of cell cultures.
Updated: 28.03.2024
The German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) has adjusted their recommendations regarding the pneumococcal vaccination during the current pandemic. Seniors of 70 years and older as well as persons with particular underlying diseases have been requested to have themselves vaccinated against pneumococci, since persons in this age group have an increased risk of SARS-CoV-2 infection. Besides, the vaccination of infants and young children up to the age of 2 years is recommended.
Most vaccines, for example individual vaccines against hepatitis A and hepatitis B as well as combination vaccines for the primary immunisation of infants and young children (against diphtheria, pertussis, tetanus, hepatitis B, polio, haemophilus influenzae type B) do not contain any chicken egg white and do therefore not present any problems for people with egg white allergy.
MMR vaccines (measles, mumps, rubella), MMRV (measles, mumps, rubella, varicella (chickenpox)), yellow fever, tick-borne encephalitis (TBE) and influenza may contain traces of egg white. If you are allergic to chicken egg white, please contact your doctor, who will carry out an individual benefit-risk assessment for you before performing a vaccination, and who can take precautionary measures during a vaccination (for example, follow-up of the vaccinee in the doctor’s office). You will find further information and answers to this question on the web pages of the Robert Koch Institute:
The Paul-Ehrlich-Institut offers a lot of information about vaccination on its website, e.g. a list of all vaccines approved in Germany: www.pei.de/vaccines.
In the last column of each table, we offer links to the pages on which the so-called technical and usage information is linked. This includes all information e.g. on the use, the contraindications and the composition of vaccines.
The package leaflet is enclosed with the drug packages and contains the most important information and instructions for patients.
The SmPC is specific to physicians and is more detailed. You can find the links to the specialist information on our vaccine list in the last column of the table by following this link: www.pei.de/vaccines.
Vaccines do not contain any pure aluminium, but certain vaccines contain aluminium compounds as an adjuvant.
Attenuated live vaccines do not require an enhancer. These include, for example, vaccines against measles, mumps, rubella and chicken pox (varicella).
Inactivated vaccines, however, such as vaccines against whooping cough, TBE (tick-borne encephalitis), meningococci, tetanus and diphtheria vaccines contain aluminium compounds as enhancers. This is necessary because such vaccines contain only killed pathogens or parts thereof that do not sufficiently stimulate the immune system without an enhancer. Here, the enhancer helps the immune system to build an effective immune protection.
The content of aluminium compounds of all vaccines authorised in Germany and Europe is well below the permitted limit specified in the European Pharmacopoeia.
Every day, every human being absorbs aluminium in the form of a chemical compound from the air, drinking water, and food. In comparison to that, the additional uptake of aluminium compounds via vaccinations in a person's life is minimal.
Today's vaccines approved in Germany are thiomersal-free, which means they are free from mercury compounds, as they are supplied in pre-filled syringes. The only exceptions are pandemic and prepandemic inactivated influenza vaccines in multi-dose containers. The latter may contain thiomersal, in the form of an organic mercury compound, as a preservative.
The quality, efficacy and safety of a vaccine are only guaranteed if the vaccine has been stored correctly. The respective summary of product characteristics (SmPC) provides information on the required storage conditions, which are documented by extensive studies. You can find the links to the SmPC on our vaccine list in the last column of the table by clicking on this link: www.pei.de/vaccines.
For many years, trivalent (3-fold) influenza vaccines were common. They contained pathogen components (components) of two virus strains of type A and of one virus strain of type B. Since 2016, tetravalent (quadrivalent or quadruple) vaccines are also available. They contain an additional type B virus strain. This provides a broader protection against circulating influenza viruses.
From the 2018/2019 season, the recommendation of the Ständige Impfkommission (STIKO, Standing Vaccination Commission) for tetravalent vaccines applies.
Background: In the last few years it has become apparent that during the flu season both lines of the B-strain circulated to an ever increasing extent. Therefore, the World Health Organization (WHO) recommends two A-type strains and two B-type strains for the composition of strains for influenza vaccines:
Recommended composition of influenza virus vaccines for use in the 2018-2019 northern hemisphere influenza season.
EU recommendation for 2019/20 seasonal flu vaccine composition
The manufacture of vaccines is complex and time-consuming. For instance, manufacturing combination vaccines with 5 or 6 components for the vaccination of infants up to the age of 2 years can take up to 2 years.
Vaccines are complex biomedical products. They are based on biological starting materials. Before a vaccine is ready to use, it undergoes hundreds of quality controls. Delays can occur in the event of problems during the production of a component, e.g. if the pathogens do not replicate as planned.
The Paul-Ehrlich-Institut provides an overview of supply shortages of vaccines on its internet pages.
www.pei.de/lieferengpaesse.
In each last column, you will find information on an alternative vaccine or a link to the notes for action provided by the Ständige Impfkommission (STIKO, Standing Vaccination Committee) at the Robert Koch-Institut (RKI).
For medical advice please contact your treating doctor. The Paul-Ehrlich-Institut is not a medical care provider like a hospital or a clinic and is not entitled to provide advice on vaccinations to individuals.
If you suspect that you are suffering from vaccination damage, you will have to make an application for recognition of your vaccination damage at the responsible Versorgungsamt (public support institution) in your federal state.
Overview of support institutions (Versorgungsämter)
Before a vaccine is marketed, it must undergo an extensive marketing authorisation procedure, either in Germany (national marketing authorisation procedure) or at the European Medicines Agency (EMA) (centralised procedure by the EU Commission).
The quality, efficacy, and safety of the vaccines are thoroughly assessed and evaluated during the authorisation procedure. A favourable benefit-risk assessment is a prerequisite for authorisation of a vaccine.
The vaccine continues to undergo regular federal testing even after authorisation. Any newly produced vaccine batch must be released by the Paul-Ehrlich-Institut after independent batch testing before it may be placed on the market in Germany.
This usually includes experimental lab testing. The Paul-Ehrlich-Institut operates as an "Official Medicines Control Laboratory" (OMCL). OMCLs take on the task of batch testing in Europe.
From Vaccine Authorisation to Recommendation by the Standing Commission on Vaccination in Germany: Criteria for the Objective Assessment of Benefits and Risks (German only)
Vaccine Testing: The Challenge of Testing Complex Combination Vaccines (German only)
The viral component or gene that provides protection against an infectious disease is called an antigen. In order to distinguish between the different types of viral vaccines, they are divided into live virus vaccines and inactivated vaccines, also known as dead vaccines. With the new mRNA vaccines came the addition of a third category, genetic vaccines.
Live virus vaccines contain an attenuated (weakened) form of the wild-type virus, which replicates in the body for a limited period after vaccination but cannot trigger the infectious disease associated with the wild-type virus. This form of the virus leads to long-lasting vaccination protection against the infectious disease. An example of live attenuated vaccines are the vaccines against measles, mumps, and rubella. All three vaccines have been combined into one measles-mumps-rubella vaccine (MMR vaccine). Thus, vaccination with the MMR combination vaccine can protect against all three infectious diseases at the same time.
Inactivated viral vaccines, also known as dead vaccines, contain the entire virus in inactivated form (inactivated whole virus vaccines) or individual virus components in a more (subunit vaccines) or less (split vaccines) purified form. Recombinant protein vaccines, i.e. those produced by genetic engineering, usually contain a virus protein that is produced in cell culture without other virus components. Most commonly, subunit, split, and recombinant protein vaccines are mixed with an adjuvant in order to stimulate both the humoral and the cellular immune response. When the virus proteins spontaneously combine to form a structure that resembles a virus particle, these are referred to as "virus-like particles" (VLPs) and are used to produce VLP vaccines. The TBE vaccine, which protects against tick-borne early summer meningoencephalitis (TBE), is an example of an inactivated vaccine.
Genetic vaccines contain the nucleic acids DNA or mRNA with the blueprint for one or more virus proteins. These vaccines are produced using DNA that is unpackaged, packaged in lipid particles, or formed as part of the genome in viral particles (known as viral vectors) that are incapable of replicating. The nucleic acids are transferred to a small number of somatic cells. After reading the antigen blueprint (antigen gene), the antigen is produced by the host somatic cells and presented to the immune system. mRNA and vector vaccines are used to vaccinate against COVID-19. Vector vaccines, which, like live virus vaccines, are limited in the body and can only replicate for a short time, are also referred to as hybrid virus vaccines. An example of this vaccine type is the VSV-EBOV Ebola vaccine, in which the gene for the envelope proteins of the vesicular stomatitis virus (VSV) has been replaced by the gene with the blueprint of the Ebola virus envelope protein.
Vaccination against an infectious disease caused by a pathogen prepares the humoral (antibody-based) and cellular (cell-based) immune systems for contact with the pathogen. The vaccination feigns contagion with the pathogen in the body without transmitting the infectious disease. This form of active immunisation trains the immune system. 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 immunity against the pathogen, the infectious disease either does not occur at all or has a milder course. Vaccine efficacy as well as quality and safety are tested during authorisation studies. A vaccine is only authorised if the benefit-risk ratio is favourable. Sufficient vaccination protection often needs to be built up by administering more than one dose of vaccine (primary immunisation). Many vaccinations wear off over time but can be extended by booster vaccinations or repeated vaccinations if necessary.
Updated: 05.10.2023
