Rather than injecting a whole pathogen to trigger an immune response, subunit vaccines (sometimes called acellular vaccines) contain purified pieces of it, which have been specially selected for their ability to stimulate immune cells. Because these fragments are incapable of causing disease, subunit vaccines are considered very safe. There are several types: protein subunit vaccines contain specific isolated proteins from viral or bacterial pathogens; polysaccharide vaccines contain chains of sugar molecules (polysaccharides) found in the cell walls of some bacteria; conjugate subunit vaccines bind a polysaccharide chain to a carrier protein to try and boost the immune response. Only protein subunit vaccines are being developed against the virus that causes COVID-19.

Other subunit vaccines are already in widespread use. Examples include the hepatitis B and acellular pertussis vaccines (protein subunit), the pneumococcal polysaccharide vaccine, and the MenACWY vaccine, which contains polysaccharides from the surface of four types of the bacteria that causes meningococcal disease joined to diphtheria or tetanus toxoid (conjugate subunit).

Subunit vaccines contain fragments of protein and/or polysaccharide from the pathogen, which have been carefully studied to identify which combinations of these molecules are likely to produce a strong and effective immune response. By restricting the immune system’s access to the pathogen in this way, the risk of side effects is minimized. Such vaccines are also relatively inexpensive and easy to produce, and more stable than those containing whole viruses or bacteria.

A downside of this precision is that the antigens used to elicit an immune response may lack molecular structures called pathogen-associated molecular patterns, which are common to a class of pathogen. These structures can be read by immune cells and recognized as danger signals, so their absence may result in a weaker immune response. Also, because the antigens do not infect cells, subunit vaccines mainly only trigger antibody-mediated immune responses. Again, this means the immune response may be weaker than with other types of vaccines. To overcome this problem, subunit vaccines are sometimes delivered alongside adjuvants (agents that stimulate the immune system) and booster doses may be required.

Update (March 2023): One protein based vaccine (Nuvaxovid / Covovax) has been granted WHO Emergency Use Listing.