Vaccines generally have two major types of ingredients, antigens and adjuvants. Antigens are designed to cause the immune system to produce antibodies and/or T-cells against a specific pathogen or its toxin. Adjuvants amplify immune responses more generally.
Pathogens (such as viruses and bacteria) are assembled from building blocks—proteins, sugars, nucleic acids (such as DNA) and fats. Each pathogen has a unique set of these building blocks. Some can be recognised by the body’s immune system and are termed antigens. The antigens used in a vaccine are designed to trigger a specific protective response by the immune system to a particular pathogen 13,39-41. Therefore, each vaccine contains a different set of antigens.
Some vaccines comprise the killed whole pathogen that the vaccine is designed to protect against. The virus or bacterium is grown in the laboratory and killed by heat and/or chemicals to render it non-infectious 42. The injectable poliomyelitis (polio) vaccine and inactivated hepatitis A vaccine are examples of this type of vaccine.
Other vaccines contain only components of the pathogen as their antigens. These components can be prepared by purifying them from the whole bacterium or virus, or by genetically engineering them 43-45. Engineered vaccines include the hepatitis B virus vaccine and the human papillomavirus vaccine, which protects against cervical cancer.
In some vaccines, sugar components of the pathogen are joined with proteins to create an antigen that can generate a stronger response—this allows even 6-week-old babies to make significant amounts of antibody, which they otherwise could not do until they are older 46. These vaccines are called conjugate vaccines, and include those against meningococcal and pneumococcal disease.
Preservatives, such as thiomersal (also known as thimerosal) and boric acid, are chemicals designed to prevent the growth of bacteria in vaccine preparations.
In practice, preservatives are no longer needed in vaccines given in Australia, as they are now produced in single-use sealed vials. The only exception is when multi-dose vials are used during an influenza pandemic as an emergency measure or for mass vaccinations.
In the past, preservatives such as thiomersal were added to vaccines. However, the quantity was very small and the total amount received by a fully vaccinated person was minuscule 53. These small amounts of preservatives have never been shown to be harmful 54.
Another group of vaccines is based on the toxin produced by the pathogen that causes the disease symptoms. The toxin is chemically treated to make it into a harmless toxoid. The antibodies produced against this toxoid are still able to neutralise the toxin, and to prevent disease symptoms from developing 47. Examples of this type include the tetanus and diphtheria vaccines.
Some vaccines contain an infectious microorganism. These are called live vaccines. The micro-organism may be derived from the pathogen (bacterium or virus) that the vaccine aims to protect against. This is usually achieved by growth of the pathogen in the laboratory under conditions designed to weaken or ‘attenuate’ it. This attenuation process permanently alters the pathogen so that it is still infectious, but is unable to cause the disease 48. Examples include the injectable MMR vaccine, the oral polio vaccine, and the chickenpox vaccine.
Because most vaccine antigens are prepared from whole organisms, a vaccine may contain some of that organism’s genetic material in the form of DNA, or a similar type of molecule known as RNA. The amount of genetic material in a vaccine is minuscule, much less than the amount we eat in our food every day 55. Vaccines based on living pathogens contain that organism’s genetic information, which is necessary for the vaccine to work. However, the DNA (or RNA) in the pathogen does not persist or lead to long-term detrimental effects in the vaccinated person 56.
Alternatively, a live vaccine may consist of a naturally occurring organism that is closely related to the pathogen, but does not cause disease in healthy humans with intact immune systems. An example is the BCG vaccine against tuberculosis and leprosy.
Vaccines containing live pathogens are not recommended for people whose immune systems are impaired due to use of immunosuppressive drugs, serious illness or genetic abnormalities of the immune system because of the risk of causing disease. Similarly, live vaccines are not recommended during pregnancy as a precautionary measure, in case the pathogens they contain cross the placenta. This is because a baby’s immune system is not completely developed until after birth (see also Box 11, Question 4). Vaccines without live micro-organisms (‘killed’ vaccines), in contrast, are not harmful in pregnancy.
Adjuvants are substances that promote a more vigorous immune response to vaccine antigens. They can also help target the body’s response. In doing so, they may cause mild local reactions (soreness, redness and swelling) at the injection site. These reactions are a healthy indicator of the strength of the underlying immune response.
Most killed vaccines incorporate adjuvants, to make the body’s defences think a significant infection is present. They stimulate stronger, longer-lasting immune responses to the vaccine antigens, leading to better protection against subsequent infection. Adjuvants are not needed in vaccines based on live organisms, as these naturally produce inflammation and amplify protective immunity.
In most human vaccines that contain adjuvants, the adjuvant is an aluminium salt (known as alum), which has a track record of safety dating back to the 1950s 49. Some newer vaccines incorporate more active adjuvants, derived from naturally occurring oil in water emulsions, fats from bacterial cell walls, or sugars. These can produce more vigorous and better targeted immune responses against the infectious agent 50.
In addition to adjuvants and antigens, vaccines can contain minute quantities of materials from the manufacturing process. These can include trace amounts of detergents, nutrients from the laboratory cultures (see Box 4 and Box 6), chemicals used to kill the pathogens, stabilisers like gelatin or small amounts of DNA (see Box 5) and parts of dead organisms.
Egg allergy is a recognised clinical problem, particularly in children.
Some vaccines, such as influenza or MMR vaccines, contain antigens from viruses grown in eggs or on chick cells, and therefore may contain some egg proteins. However, newer MMR vaccines contain so little egg protein that it is now conclusively considered to be safe to give them even to someone who is already known to be very sensitive to egg protein 57. The seasonal influenza vaccines in current use contain minimal amounts of egg protein and can be used in most egg sensitive children 58.
The viruses in two other less frequently used vaccines (for Q fever and yellow fever) are also grown in eggs, and specialist advice should be sought if either of these vaccines is needed for a person with severe egg allergy. Specialist advice should also be sought if there is any suggestion of allergy to the trace amounts of gelatin present in the above vaccines.
Vaccine developers are required by regulatory authorities to test for the presence of these extra materials during the manufacturing process to ensure they do not exceed levels known to be safe 1,51 (see Question 4)
Occasionally, individuals can be allergic to an ingredient of a vaccine, although such reactions are rare. Fewer than one in 100,000 vaccine doses delivered cause a significant allergic reaction 52 (see Box 6).
© 2021 Australian Academy of Science