All vaccines work by exposing the body to molecules from the target pathogen to trigger an immune response – but the method of exposure varies.
Whole Virus vaccine
Whole virus vaccines use a weakened (attenuated) or deactivated form of the pathogen that causes a disease to trigger protective immunity to it. There are two types of whole virus vaccines. Live attenuated vaccines use a weakened form of the virus, which can still grow and replicate, but does not cause illness. Inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals or radiation so they cannot infect cells and replicate, but can still trigger an immune response. Both are tried and tested vaccination strategies, which form the basis of many existing vaccines – including those for yellow fever and measles (live attenuated vaccines), or seasonal influenza and hepatitis A (inactivated vaccines). Bacterial attenuated vaccines also exist, such as the BCG vaccine for tuberculosis.
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 (polysaccharide), and the MenACWY vaccine, which contains polysaccharides from the surface of four types of the bacteria which causes meningococcal disease joined to diphtheria or tetanus toxoid (conjugate subunit).
Viral vector-based vaccines differ from most conventional vaccines in that they don’t actually contain antigens, but rather use the body’s own cells to produce them. They do this by using a modified virus (the vector) to deliver genetic code for antigen, in the case of COVID-19 spike proteins found on the surface of the virus, into human cells. By infecting cells and instructing them to make large amounts of antigen, which then trigger an immune response, the vaccine mimics what happens during natural infection with certain pathogens - especially viruses. This has the advantage of triggering a strong cellular immune response by T cells as well the production of antibodies by B cells. An example of a viral vector vaccine is the rVSV-ZEBOV vaccine against Ebola
Nucleic acid vaccines use genetic material from a disease-causing virus or bacterium (a pathogen) to stimulate an immune response against it. Depending on the vaccine, the genetic material could be DNA or RNA; in both cases it provides the instructions for making a specific protein from the pathogen, which the immune system will recognise as foreign (an antigen). Once inserted into host cells, this genetic material is read by the cell’s own protein-making machinery and used to manufacture antigens, which then trigger an immune response. This is a relatively new technology, so although DNA and RNA vaccines are being developed against various diseases, including HIV, Zika virus and COVID-19, so far none of them have yet been approved for human use. Several DNA vaccines are licenced for animal use, including a horse vaccine against West Nile virus.