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

Covid-19, the disease caused by the SARS-CoV-2 coronavirus, affects people all over the world. However, companies and research institutes are developing vaccines. Four vaccines have now been approved in the EU, and partial registration dossiers have already been submitted for four others.

Globally, at least 341 vaccine projects are moving forward (those for already approved vaccines included): the World Health Organization (WHO ) currently counts 329 (as of Nov. 30, 2021). In addition, there are at least twelve more projects that it does not yet list (1)

In addition, the WHO is considering whether the CODI-VAC vaccine from Codagenix/Serum Institute of India (USA/India), which is administered as a nasal drop, should also be tested as part of the Phase III "Solidarity Trial Vaccines" study. The vaccine contains replication-capable vector viruses based on influenza viruses. To date, it has completed a Phase I trial.

Ongoing projects in earlier stages of development can be found in the continuously updated table "COVID-19 Landscape of novel coronavirus candidate vaccine development worldwide" of the World Health Organization WHO.

Among others, these vaccine projects have been terminated prematurely after clinical trials: University of Queensland and CSL projects, Altimmune, MSD/Institute Pasteur/University of Pittsburgh, MSD/IAVI, Sanofi/Translate Bio, and CureVac. In one case, the vaccine appropriately stimulated the immune system but led to false positive results on HIV tests. Several other vaccines did not achieve a sufficiently strong immune response. In one case, the company decided not to complete development of its own mRNA vaccine in view of the competitive situation. In each case, this led to the decision to discontinue the project in question.

The companies have made great efforts in parallel with clinical development to also enable large-scale production of their vaccines. There is more on this in the article"Expanding supply volumes for Covid-19 vaccines". The main organization for global distribution of the vaccines, especially to poorer countries, is the COVAX facility. More can be found here.

The first vaccines against covid-19 licensed in the EU are based on mRNA or vector viruses. Among the vaccines still in development, there are vaccines of the same type as well as vaccines that are still of a different type. Here is an overview of the most important vaccine types:

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

Vaccines with viral protein: These are also called subunit vaccines and are counted among the "dead vaccines" because they do not contain any living viruses. These vaccines contain a few micrograms of a selected protein from SARS-CoV-2. Technically, however, the protein is not obtained directly from the coronavirus, but is produced by genetic engineering. Examples are the vaccines from Novavax and Sanofi / GSK. Typically, vaccines with viral protein also contain an adjuvant that puts the immune system on alert immediately after vaccination. This makes the immune system particularly aware of the injected foreign protein and builds up a defence against it; this defence can then also fight the actual viruses. Vaccines containing viral protein have already proved effective against other diseases, such as hepatitis B and influenza (although here the protein is extracted directly from the viruses). So far, no vaccine with viral protein against covid-19 has been approved in the EU, but two are under rolling review by the EMA.


mRNA vaccines: these vaccines contain the associated gene for a viral protein instead of a selected viral protein; and they are 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 appropriate proteins. They use an externally supplied mRNA in the same way as they use 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 just as vaccines with viral protein do (well illustrated by #EUmythbusters). mRNA vaccines have the advantage that the manufacturing process is always the same, regardless of the pathogen; so you save development time for the production process.
Two mRNA vaccines against covid-19 are already licensed in the EU (by BioNTech/Pfizer and by Moderna). Others are in development.


DNA vaccines: Similar to mRNA vaccines, DNA vaccines are also expected to work. In these, 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 are used to produce viral protein, which then works in the same way as a vaccine with viral protein. So there are even more steps involved in achieving the vaccine effect than with mRNA vaccines; and special inoculation devices are needed to get the DNA into the cells in the first place. One advantage over mRNA vaccines, however, is that DNA is more stable and DNA vaccines therefore require less refrigeration. In India, the company Zydus Cadila 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 been applied for yet. Other DNA vaccines against Covid-19 are also in development. Inovio is currently testing its DNA vaccine in a WHO Phase III trial and is preparing its own Phase III trial (INNOVATE). The OpenCorona consortium, led by the Swedish Karolinska Institute and involving the Universities of Giessen and Tübingen, is also working on a DNA vaccine.

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 immunising 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. More on this can be found in the article"Next-generation corona vaccines".

In addition, there are also projects aimed at an orally applicable vaccine. Examples: