Vaccine manufacture and composition is complex and tightly regulated to maximise potency and safety. The safety of the individual components, and of the vaccine itself, in the amounts administered, must be demonstrated before a vaccine can be approved for use in New Zealand.
What is in a vaccine?
All vaccines contain an active component (the antigen) which generates the protective immune response.
If required, vaccines may also contain additional components.
- Buffers and ionic compounds
An adjuvant encourages a stronger immune response to the vaccine antigen. In New Zealand, some vaccines contain a tiny amount of aluminium salts, such as aluminium hydroxide, aluminium phosphate, and potassium aluminium sulphate (alum), to act as an adjuvant.
Aluminium adjuvants work by helping to retain the antigen at the injection site long enough for an immune response to be generated and by inducing immune system cells and a range of inflammatory factors to the local injection site to enhance the immune response. Generally, the use of aluminium adjuvants in vaccines means that less antigen is required, or, with some vaccines, fewer doses are needed. Most current inactivated and protein-based, and some protein-conjugated polysaccharide, vaccines use aluminium salts in some form.
We are born with some aluminium already stored in our body and continue to add to our aluminium stores through eating, drinking, and some medicines. Vaccines contribute very little to this and are given infrequently. Even though we regularly consume food and drinks containing aluminium throughout our lifetime, only a small amount of aluminium travels into the blood stream from digestion, the rest comes out in faeces. Most of the aluminium that enters our blood stream is quickly processed and removed by the kidneys in urine. The small amount that stays in our body is mainly stored in our bones, with some stored in our lungs and brain.
Use of aluminium salts in vaccines as a long and impressive safety record. Some studies have found aluminium containing vaccines to be associated with local reactions and, less often, with the development of subcutaneous nodules at the injection site. This is particularly so if the injection is given too superficially. Other studies have reported fewer reactions with aluminium containing vaccines than those without. This depends on the overall vaccine formulation.
A review of all he available studies of aluminium-containing diphtheria, tetanus and pertussis vaccines (either alone or in combination) did not find any evidence that aluminium salts in vaccines cause serious or long-term adverse events.
Emulsion adjuvants are not in any vaccines currently used in New Zealand. Emulsion adjuvants are made from an oil-in-water, such as squalene, DL-a-tocopherol (vitamin E), or lipids from the Salmonella minnesota bacterium or Quillaja saponaria tree. Overseas vaccines may include AS01B, AS01E, AS03, AS04, or MF59 as an emulsion adjuvant.
The CpG-ODN nucleotide adjuvant is not in any vaccines currently used in New Zealand. The adjuvant is a man-made molecule copying a pattern of molecules found in bacterial DNA that enhance an immune response.
Excipients are all substances in the finished product, other than the active ingredients. Excipients may have been used during the manufacturing process or in the finished pharmaceutical product to maintain quality.
Buffers and ionic compounds
Buffers serve to resist changes in pH, such as monopotassium phosphate and sodium borate. Ionic compounds adjust tonicity and maintain osmolarity. Sodium chloride (table salt) is the most common ionic compound used.
Preservatives stop unwanted contamination of a vaccine. They have been used in vaccines for many years. Very few serious adverse events have been associated with the use of these preservatives. The most commonly used preservative is 2-phenoxyethanol.
2-phenoxyethanol is used in a range of cosmetics such as baby care products, eye and ear drops as well as vaccines. It is metabolised (broken down) and excreted by being exhaled, in the urine and in the faeces, and has little toxicity in humans. There is little toxicity in humans and some irritation with very high doses in animals.
Phenol is an aromatic alcohol infrequently used as a preservative in vaccines.
No vaccines on the New Zealand Immunisation Schedule contain thiomersal, also called thimerosal. Thiomersal is a mercury derived compound that was used as a preservative in vaccines and other health care products internationally for many years. There is no evidence that thiomersal caused any serious or long-term adverse events.
Residuals are the remaining minute quantities of substances that have been used during the manufacturing or production process of individual vaccines. Residuals depend on the process used, which may have involved cell culture mediums, egg proteins or other animal derived ingredients, culture cells, yeast, antibiotics such as neomycin or streptomycin, or inactivating agents such as formaldehyde. These substances are only present as traces and often measured as parts per million and parts per billion in the final vaccine formulation.
Stabilisers stop chemical reactions from occurring in the vaccine and prevent the components from separating from each other or sticking to the vaccine vial during transportation and storage. Examples of stabilisers include sugars such as lactose and sucrose, amino acids such as glycine and monosodiumglutamate (salts of amino acids), proteins such as recombinant human albumin (Recombumin®) derived from baker’s yeast or fetal bovine (cow) serum and gelatin, partially hydrolysed collagen usually of porcine (pig) but can be of bovine origin.
Surfactants are a type of emulsifier. They assist particles remain suspended in liquid, preventing settling and clumping, by lowering the surface tension of the liquid. An example is polysorbate 80 (Tween 80®), made from sorbitol (sugar alcohol) and oleic acid (omega-9 fatty acid), which is also used in foods such as ice cream. Surfactants are also used in shampoos, toothpastes, inks and fabric softeners.
A diluent is a liquid used to dilute a vaccine to the proper concentration immediately prior to administration. This is usually sterile water.
A solvent is a substance that dissolves another substance, creating a solution. The most common solvent used in everyday living, and vaccine manufacture, is water.
Animal derived products
Some people have concerns about animal derived products such as gelatin in vaccines. This may be for faith-based reasons or concerns about the safety of animal derived products. More information on animal derived products in vaccines can be found in the fact sheet Animal derived products and National Immunisation Schedule vaccines on our Written Resources webpage.
- 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.