Vaccines to protect against Covid-19, the new coronavirus infection

Even though the pandemic is officially over, people around the world are still contracting Covid-19. The WHO and other health institutions are therefore advising at least certain population groups to receive booster vaccinations. There is also hope that in the future, vaccines will not only protect against a severe course of the disease, but even against infection, and ideally even with regard to different corona viruses. That is why companies and research institutes are continuing to work on corona vaccines.

While some projects are still working on a first-generation vaccine, other companies and institutes are already working on second-generation vaccines that will provide even better protection against new SARS-CoV-2 variants or ensure that vaccinated individuals no longer transmit the virus, even symptom-free. This is explained in a separate article.

Numerous Covid-19 vaccine projects were initiated in Germany during the pandemic. But only one has produced an approved Covid 19 vaccine so far: the project by BioNTech and collaboration partner Pfizer for an mRNA vaccine. But projects for other vaccines are underway in Germany by the following companies and research institutions:

In addition, the following companies and research institutes are involved in supporting vaccine production:

Vaccines against covid-19 approved in the EU are based on mRNA, vector viruses, selected proteins, or killed coronaviruses. Other types have been approved in other regions; and more are in development. Here is an overview of the main vaccine types:

You can also download this chart as a PDF or as a JPG (free to use with attribution).

Protein-based vaccines: these are also called subunit vaccines and, according to some definitions (see below), are counted among the dead vaccines because they do not contain live viruses. These vaccines contain a few micrograms of a selected protein from SARS-CoV-2, but technically the protein is not derived directly from the coronavirus but is produced by genetic engineering. Examples include vaccines from Novavax (approved), Sanofi / GSK, and Texas Children's Hospital / Baylor College / Biological E (approved in India). Typically, vaccines with viral protein still contain an effect enhancer (adjuvant), which puts the immune system on alert immediately after vaccination. This makes it particularly alert to the injected foreign protein and builds up a defense against it; this can then also fight the actual viruses. Vaccines containing viral protein have already proved effective against other diseases, such as hepatitis B and influenza (in the latter case, however, the protein is usually obtained directly from the viruses).


mRNA vaccines: Instead of a selected viral protein, these vaccines contain the associated gene for it; and they do so in the form of an mRNA (messenger RNA) embedded in small vesicles (lipid nanoparticles) that protect them and allow them to enter cells. For cells, mRNAs are something commonplace; they constantly create mRNA transcripts of genes in the nucleus for themselves when they want to make the corresponding proteins. They use an externally supplied mRNA just as they would their own: they use it several times to make the protein described in it and then degrade it. In this way, viral protein is produced in the body after vaccination, which then activates the immune system in exactly the same way as vaccines with viral protein do (well illustrated by #EUmythbusters). mRNA vaccines have the advantage that the production process is always the same, regardless of the particular pathogen; thus, one saves development time for the production process. Two mRNA vaccines against Covid-19 are licensed in the EU (from BioNTech/Pfizer and from Moderna), plus several versions of these vaccines adapted to virus varieties. Other mRNA vaccines are licensed or under development in other regions of the world.


DNA vaccines: Similar to mRNA vaccines, DNA vaccines also work. In them, the gene for a viral protein is contained on a piece of DNA (for example, on a DNA ring [= plasmid]). After vaccination, the piece of DNA has to enter cells; and the cells then have to make transcripts from it into mRNA, which in turn is used to make viral protein, which then works as in a vaccine with viral protein. Thus, even more steps are required here to achieve the vaccine effect than with mRNA vaccines; and special inoculation devices are required for the DNA to enter the cells in the first place. One advantage over the mRNA vaccines approved to date, however, is that DNA is more stable and DNA vaccines therefore require less refrigeration. In India, the company Zydus has received approval for the first DNA vaccine against Covid-19, called ZyCoV-D (in fact, it is the world's first DNA vaccine ever); however, no EU approval has yet been applied for. In addition, Sweden's Karolinska Institute is also developing a DNA-based Covid-19 vacc ine and is currently testing it in a Phase I trial with volunteers.


Vector virus vaccines: As with mRNA and DNA vaccines, the aim of vector vaccines is to induce body cells to produce a SARS-CoV-2 protein by introducing a gene, which then stimulates a defense response in the immune system (1) . However, the gene in question is introduced into the cells here with the help of another, harmless virus. Such harmless viruses, which are suitable as carriers, are called vector viruses. Examples are some adenoviruses from chimpanzees or gorillas and the "Modified Vaccinia Virus Ankara" (MVA). Vector vaccines against Covid-19 from AstraZeneca and Janssen are licensed in the EU. The Russian Gamaleya Institute's Sputnik V vaccine is under rolling review at the EMA. Other vector vaccines are in development, such as an inhalable vaccine by the German Center for Infection Research (DZIF) with IDT Biologika and a nasal vaccine by the University Hospital Erlangen. Prime Vector Technologies (Tübingen) and Speransa Therapeutics are also working on a vector vaccine. Even before the Corona pandemic, there were approved vector virus vaccines against Ebola.


Vaccines with inactivated SARS-CoV-2 viruses: such vaccines are based on one of the oldest principles of vaccine production: In principle, SARS-CoV-2 viruses themselves (produced in cell cultures) are used as vaccines to stimulate a protective immune response. The only difference is that they are previously damaged ("killed") in such a way that they are no longer capable of replication. This can be done with different techniques. Such vaccines are classified as inactivated vaccines by all the different definitions. One example is the EU-approved vaccine VLA2001 from Valneva.


Vaccines containing attenuated SARS-CoV-2 viruses: Attenuated viruses are viruses that can infect and replicate in humans, but only slowly. Thus, they cannot cause severe symptoms but can cause an immune response. Vaccines of this type have long been used against mumps, measles and rubella, among others. Now such vaccines are also being developed against Covid-19, among others by the Free University of Berlin in conjunction with the Universities of Bern and Geneva (Switzerland), the Friedrich Loeffler Institute, and RocketVax (Switzerland).


Peptide vaccines: Such vaccines are similar to vaccines containing viral protein - for example, they do not contain genetic material, but they do contain an effect enhancer (adjuvant). But instead of whole proteins, they contain only small fragments of them. These are particularly well suited to stimulating a protective defense response by T cells (a specific type of immune cell) after vaccination. This is of importance for people who cannot produce antibodies well due to cancer chemotherapy or congenital immunodeficiency and therefore rely on their T cells for a viral defense. No such vaccine has yet been approved in the EU, but the University of Tübingen (CoVac-1), among others, is working on it and has thus reached phase II.

There are also differences in the forms of application. Although most projects are aimed at injectable vaccines, there are exceptions. For example, the development of vaccines that can be administered via the nose is linked to the hope of immunizing people in such a way that they are not only protected against an outbreak of the disease themselves, but also that they can no longer infect anyone else with SARS-CoV-2. One of these projects is being pursued by the University Hospital Erlangen (see above). Animal experiments have been positive. More on this topic can be found in the article"Next generation corona vaccines".