Vaccines contain tiny fragments of the disease-causing organism, or the ‘instructions’ for making those fragments. They also contain other ingredients to keep the vaccine safe and effective. The latter are included in most vaccines and have been used for decades in billions of doses of vaccines.
Each component in a vaccine serves a specific purpose, and each ingredient undergoes several tests during the manufacturing process. In this process the safety of all ingredients is verified
All vaccines contain an active component, (the antigen,) that generates an immune response, or the instructions for producing that active component. The antigen can be a small part of the disease-causing organism, for example a protein or sugar, or the whole organism attenuated or inactivated.
Preservatives prevent the vaccine from becoming contaminated when a vial that will be used to vaccinate more than one person is opened. Some vaccines do not have preservatives because they are stored in single-dose vials that are discarded after administration. The most commonly used preservative is 2-phenoxyethanol. It has been used for many years in some vaccines, as well as in a number of child care products, and its use in vaccines is safe because it has very low toxicity in humans.
Stabilizers prevent chemical reactions from occurring in the vaccine and prevent the vaccine components from sticking to the vial.
Stabilizers can be sugars, (lactose, sucrose,) amino acids, (glycine,) gelatin, and proteins, (recombinant human albumin, derived from yeast).
Surface-active substances keep all the ingredients of the vaccine mixed. These substances prevent the elements in the liquid form of the vaccine from settling or clumping together. They are also often used in foods, for example, ice cream.
Residual substances are tiny amounts of various substances used during the manufacturing or production of the vaccine, which are not active ingredients in the final vaccine. Substances will vary depending on the manufacturing process used, and may include egg proteins, yeast, or antibiotics. The residual traces of these substances that could be found in a vaccine are so minute that they must be measured as parts per million or parts per billion.
A diluent is a liquid used to dilute a vaccine to the correct concentration, immediately before use. The most widely used diluent is sterile water.
Also, some vaccines contain adjuvants. An adjuvant enhances the immune response to the vaccine, either by retaining the vaccine at the injection site for a little longer, or by stimulating local immune cells.
The adjuvant can be a minute amount of aluminum salts, (e.g., aluminum phosphate, aluminum hydroxide, or potassium alum). Aluminum has been shown not to cause any long-term health problems; in fact, people commonly ingest aluminum through food and drink.
How are vaccines developed?
Most vaccines have been used for decades, and millions of people have safely received them each year. Like all drugs, each vaccine must undergo extensive and rigorous testing to ensure its safety before being introduced into a national vaccination program.
Above all, each vaccine in development must undergo research and evaluation to identify the antigens that should be used to generate an immune response. This pre-clinical phase is done without testing in humans. An experimental vaccine is initially tested in animals, in order to assess its safety and its chances of preventing disease.
If the vaccine elicits an immune response, it is tested in human clinical trials, in three phases:
The vaccine is administered to a small number of volunteers in order to assess its safety, confirm that it elicits an immune response, and determine the correct dose. In this phase, vaccines are generally tested in healthy young adult volunteers.
The vaccine is administered to several hundred volunteers, in order to further evaluate its safety and its ability to elicit an immune response. The participants in these trials have the same characteristics, (e.g. age, gender,) as the people who are expected to be vaccinated. In this phase, multiple trials are usually conducted to evaluate different age groups and different vaccine formulations. Generally, this phase includes a group that is not vaccinated, with a view to making comparisons and determining whether changes in the vaccinated group are attributable to the vaccine or have occurred by chance.
The vaccine is administered to thousands of volunteers – and comparisons are made with a similar group of people who were not vaccinated but received a comparator product – in order to determine if the vaccine is effective against the disease and to study its safety in a group of many more people. Phase 3 trials are typically conducted in many countries and in many locations within each country to ensure that conclusions regarding the efficacy of the vaccine are valid for many different populations.
During the phase 2 and phase 3 trials, the volunteers and the scientists conducting the study do not know which volunteers are given the vaccine and to whom the comparator product is given. This is known as a ‘double-blind trial’, and it is necessary to ensure that in their evaluations of the safety or efficacy of the vaccine, neither volunteers nor scientists are influenced by knowing who received which product. Once the trial is completed and all the results are obtained, it is revealed to the volunteers and the scientists who conducted the trial, who received the vaccine and who received the comparator.
Once the results of all these clinical trials are available, a series of steps must be taken, including efficacy and safety reviews to obtain regulatory and public health regulatory approvals. The authorities in each country will carefully examine the study data and decide whether to authorize the vaccine for use. Before introducing a vaccine into a national immunization program, its safety and efficacy must be demonstrated in a wide population. The demands on the safety and efficacy of vaccines are extremely high, given that vaccines are administered to healthy and disease-free people.
After the introduction of the vaccine, constant monitoring is carried out. There are systems for monitoring the safety and efficacy of all vaccines. This enables scientists to understand the effects and safety of the vaccine even when used in large numbers of people over a long period of time. This data is used to modify policies regarding the use of the vaccine in order to optimize its effects and allow strict monitoring of the vaccine while it is being used.
Once a vaccine has been introduced, continuous monitoring is required to ensure that it remains safe.