There are many approaches to vaccine development, but vaccines can be broadly classified by how the antigen(s), the active component(s) that generate a specific immune response against the disease-causing organism, are prepared. Vaccines may be viral (live or inactivated), viral vector, subunit (protein or polysaccharide) or nucleic acid (DNA or RNA). Combination vaccines may include inactivated, protein-based and/or protein-conjugated polysaccharide vaccine components. Other ingredients in vaccines vary depending on the manufacturing process and the nature of the antigen(s).
There has been an increased focus on vaccine development using the viral-vector and nucleic-acid based platforms since the appearance of the SARS-CoV-2 virus and COVID-19 disease in late 2019.
The virus or bacteria is functional/alive but has been weakened so it can replicate in the body several times and generate an immune response without causing the disease, e.g. chickenpox, measles, mumps and rubella, rotavirus, and shingles vaccine viruses. The BCG vaccine contains live weakened tuberculosis bacteria.
After immunisation, the weakened vaccine viruses or bacteria replicate (grow) in the vaccinated person. This means a relatively small dose of virus or bacteria can be given in order to stimulate an immune response.
Live attenuated vaccines do not usually cause disease in vaccine recipients who have a healthy immune system. If a live attenuated vaccine does cause disease, e.g. chickenpox disease from the vaccine virus, it is usually more mild than disease caught from another person in the community.
If administered to a person who has an impaired immune system response, e.g. they have leukaemia or HIV infection, or are taking immunosuppressing medications, administration of a live attenuated vaccine may cause severe disease as a result of uncontrolled replication (growth) of the vaccine virus.
Inactivated vaccines do not contain live viruses or bacteria. Viruses in these vaccines are inactivated or split, e.g. polio or influenza vaccines in New Zealand, and bacteria killed. New Zealand does not have a killed bacteria vaccine on the Immunisation Schedule, but a travel-related vaccine is available for purchase. They cannot cause the disease but the inclusion of adjuvants (immune enhancers) in the vaccine help generate an immune response.
These types of vaccine can be safely given to a person with an impaired immune system response. However, a person with an impaired immune system response may not develop the same amount of protection after immunisation as a healthy person receiving the vaccine.
Inactivated vaccines usually require multiple doses. Some inactivated vaccines may also require periodic supplemental doses to increase, or ‘boost’ protection against disease.
Hepatitis A, influenza and polio vaccines are inactivated virus vaccines on the New Zealand Immunisation Schedule.
These vaccines present proteins or sugars derived from the disease-causing organism.
Protein vaccines may include fragments extracted from a virus or bacteria such as inactivated bacterial toxoid proteins, e.g. tetanus and diphtheria vaccines, or be engineered without the disease-causing organism, e.g. virus-like particles in hepatitis B and human papillomavirus (HPV) vaccines.
Protein vaccines may also include bacterial sugar/carbohydrate (polysaccharide) molecules that are joined (conjugated) to proteins, e.g. Haemophilus influenzae type b (Hib), meningococcal and pneumococcal conjugate vaccines. The immune system of infants and young children is not able to generate a useful immune response to the sugar molecules on these bacteria, which is one reason why their risk of disease and complications is so high. Joining (conjugating) each sugar molecule to a protein helps their immune system can generate a protective immune response. These vaccines also generate an excellent immune response in adults. Protein vaccines cannot cause the disease and the inclusion of adjuvants in some vaccines help generate an immune response.
Some vaccines only include sugar/carbohydrate (polysaccharide) molecules found on the outside of some bacteria, e.g. some vaccines to protect against pneumococcal or typhoid disease. This type of vaccine can generate a protective immune response in older children and adults and cannot cause the disease.
At present, different types of nucleic-acid vaccines are in developmental, pre-clinical and clinical evaluation phases, e.g. for prevention of human immunodeficiency virus (HIV), influenza and malaria diseases and treat some cancers. This vaccine platform is also being used to develop vaccines to prevent COVID-19 disease.
Nucleic acid-based vaccines use the hosts own cell machinery to make the antigen, which is then presented to the immune system. While RNA is encapsulated into lipid nanoparticle and injected, DNA is fired directly in the host cells using a brief electrical pulse.
Ahmed SS, Ellis RW, Rappuoli R. Technologies for making new vaccines. In: Plotkin S, Orenstein W, Offit P, Edwards K, editors. Plotkin’s Vaccines. 7th ed. Philadelphia: Elsevier; 2018. p. 1283-304.
Ameratunga R, Gillis D, Gold M, Linneberg A, Elwood JM. Evidence refuting the existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA). J Allergy Clin Immunol Pract. 2017;5(6):1551-5.e1.
Callaway E. The race for coronavirus vaccines: A graphical guide. Nature. 2020;580(7805):576-7.
Comberlato A, Paloja K, Bastings MMC. Nucleic acids presenting polymer nanomaterials as vaccine adjuvants. J Mater Chem B. 2019;7(41):6321-46.
Finn TM, Egan W. Vaccine additives and manufacturing residuals in vaccines licensed in the United States. In: Plotkin S, Orenstein W, Offit P, Edwards K, editors. Plotkin’s Vaccines. 7th ed. Philadelphia: Elsevier; 2018. p. 75-83.
Garcon N, Friede M. Evolution of adjuvants across the centuries. In: Plotkin S, Orenstein W, Offit P, Edwards K, editors. Plotkin’s vaccines. 7th ed. Philadelphia: Elsevier; 2018. p. 61-74.
Gomez P, Robinson J. Vaccine manufacturing. In: Plotkin S, Orenstein W, Offit P, Edwards K, editors. Plotkin’s Vaccines. 7th ed. Philadelphia: Elsevier; 2018. p. 51-60.
Harandi AM, Davies G, Olesen OF. Vaccine adjuvants: Scientific challenges and strategic initiatives. Expert Rev Vaccines. 2009;8(3):293-8.
Karwowski MP, Stamoulis C, Wenren LM, Faboyede GM, Quinn N, Gura KM, et al. Blood and hair aluminum levels, vaccine history, and early infant development: A cross-sectional study. Acad Pediatr. 2018;18(2):161-5.
Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine 2011; 29:9538-9554.
Nanishi E, Dowling DJ, Levy O. Toward precision adjuvants: Optimizing science and safety. Curr Opin Pediatr. 2020;32(1):125-38.
Shi S, Zhu H, Xia X, Liang Z, Ma X, Sun B. Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity. Vaccine. 2019;37(24):3167-78.