Nuvaxovid – the new subunit SARS-CoV-2 vaccine

After the approval of the mRNA vaccines Corminaty (Biontech/Pfizer), Spikevax (Moderna) and the vector-based vaccines Vaxzevria (Astra Zeneca) and Covid-19 Vaccine Janssen, a further SARS-CoV-2 vaccine was approved by the European Medical Agency (EMA) in December 2021. This vaccine, called Nuvaxovid, produced by the company Novavax, is a so-called subunit vaccine and differs from the previously approved vaccines.

What are subunit vaccines?

Subunit or protein-based vaccines contain only single parts of the pathogen, as for example proteins, peptides or polysaccharides. These subunits are generated either by chemical destruction of the pathogen or by recombinant technology. In the process of recombinant production the gene of the distinct subunit is integrated in bacteria, yeast or insect cells. These host cells then produce the desired subunit at high concentrations and can then be purified from the host cells. The application of subunit vaccines is nothing new. Approved subunit vaccines are in use since 1970, for example against influenza, hepatitis A/B, meningococcus or pneumococcus [1].

Subunit vaccines are safe in use as they contain only parts of the pathogen, which cannot replicate and cannot induce the disease itself. A limitation however, is the weak stimulation of the T-cell immune response, which is important for the induction of neutralizing antibodies. Thus, so called adjuvants are added to these kind of vaccines.

What are adjuvants?

An adjuvant is a substance that is added to a vaccine to stimulate and increase the immune response. These substances bind to specific cells of the innate immune system, leading to the activation of the T-cell mediated immune response. In use as adjuvants are for example different aluminium salts, emulsions, nanoparticles or lipid A analogs.

What comprises the Nuvaxovid vaccine?

The subunit that is used here as vaccine is the spike protein (S) of SARS-CoV-2. This protein mediates the binding of the virus to the cell surface and is thus responsible for the infection of the cells. The subunit in the vaccine Nuvaxovid is produced recombinant in Sf9-insect cells. Therefore, the gene of the spike-protein is inserted into a virus (baculovirus) that can infect insect cells. After infection of the Sf9 insect cells, the modified baculovirus releases the gene into the insect cells, where the protein is then produced in large amounts. To enhance the immune response of the purified S-protein the adjuvant Matrix-M1^TM is added to the vaccine. This adjuvant consists of nanoparticles formulated of saponin, a substance from the soap bark tree, cholesterol and phospholipids [2]. This formulation enhances and stimulates the immune system to produce neutralizing antibodies against the spike-protein, avoiding the binding of the virus to the cell surface.

Comparison with other vaccines

There are still more vaccines against SARS-CoV2 in clinical trials, amongst others the inactivated virus vaccines COVID-19 Vaccine (Vero Cell) Inactivated and VLA2001. Both are based on a distinct vaccine technology, and so even more different vaccine types against SARS-CoV-2 will be soon available.

[1] Pollard, A.J., Bijker, E.M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol 21, 83–100 (2021). https://doi.org/10.1038/s41577-020-00479-7

[2] Nuvaxovid (COVID-19 vaccine (recombinant, adjuvanted)). EMA/717890/2021. © European Medicines Agency, 2021

Carmen Nußbaumer
Senior Lecturer
Biotechnology & Food Technology
+43 512 2070 – 3804
carmen.nussbaumer@mci.edu