Why do some vaccines have a long list of components?
Many people will be familiar with the concept that a vaccine against a particular virus will contain a small amount of the pathogen or a part of it, at least.
When we receive the vaccine, the viral interloper triggers our immune system to launch a series of events that leave us protected against the pathogen in the future.
But a glance at the ingredients in common vaccines reveals a long list of other components, the roles of which might not seem so clear cut.
What is the purpose of the likes of gelatin, thimerosal, and Polysorbate 80? And why do some vaccines contain aluminum?
In this Special Feature article, we look at the active and inactive ingredients that make their way into vaccines and reveal what their role is in protecting us from infectious diseases.
Our immune system and active ingredients
The active ingredient in a vaccine is usually made from the viral or bacterial pathogen itself. There are two different approaches to this, with the pathogen being either alive or inactivated.
Vaccines that incorporate living bacteria or viruses are called live attenuated vaccines. The pathogen is weakened to prevent it from causing the disease, but it is still able to elicit a strong immune response.
Live attenuated vaccines work very well, but they are not suitable for everyone. If a person is immunocompromised, they may contract the very disease from which the vaccine should be protecting them.
Many vaccines, therefore, use an inactivated version of the active ingredients, which can take the form of whole bacteria or viruses that have been killed.
However, most vaccines are actually acellular, which means that they do not contain the whole pathogenic organism. Instead, they are made from parts of the pathogen, such as proteins or sugar molecules. Our bodies recognize these molecules as foreign and mount an immune response.
Examples of acellular vaccines are:
- toxoid vaccines that contain inactivated toxins from pathogenic bacteria
- conjugate vaccines made from a combination of pathogen-specific sugar molecules and toxoid proteins, as the sugars themselves do not cause sufficiently strong immune responses
- recombinant vaccines made by using bacteria or yeast cells to make many copies of specific molecules from the pathogen
Aside from the active ingredient, vaccines contain many other things. The technical term for these is excipients.
Excipients include preservatives and stabilizers, traces of things that were used to produce the vaccine, and adjuvants.
Adjuvants make vaccines stronger
Although many vaccines contain active ingredients that are strong enough to kick our immune system into gear, some need a little bit of extra help to be effective.
Adjuvants are compounds that elicit a strong immune response, improving how well a vaccine works.
Examples of adjuvants include:
- biological molecules, such as components isolated from bacteria and synthetic DNA
Aluminum is a naturally occurring metal that has many uses aside from its adjuvant properties. Cans, foil, and some window frames contain aluminum.
Aluminum salts are also used in the food industry as additives.
As an adjuvant, aluminum has a long history going back to the 1930s. Despite its widespread use, some scientists believe that the metal can cause damage to the nervous system and promote autoimmunity.
However, many experts disagree with this assessment, pointing out that some of the research implicating aluminum has been retracted.
The Food and Drug Administration (FDA) published a study in 2011 in the journal Vaccine, which concluded that "episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns."
Another example of an adjuvant is squalene, a naturally occurring oil.
The Fluad vaccine, a flu vaccine licensed for adults aged 65 years and older, contains an adjuvant called MF59, which is an oil-in-water emulsion containing squalene. The squalene used in MF59 is purified from shark liver oil.
In 2000, a research team pointed to a link between squalene and Gulf War Syndrome, prompting fears about the safety of this adjuvant.
Preservatives, stabilizers, and emulsifiers
The number of excipients in any particular vaccine varies and is highly dependent on both the manufacturing process and the vaccine's intended use.
Thimerosal is a preservative primarily used in vaccines that come in multidose vials. Thimerosal kills bacteria and fungi that may contaminate a vaccine.
It is an organic compound containing about 50% mercury, prompting some people to be concerned about exposure to this heavy metal.
According to the FDA, the amount of mercury in a standard dose of a thimerosal-containing vaccine is about the same as that in a 3 ounce can of tuna.
Gelatin is a stabilizer used in some vaccines to protect the active ingredient. It is usually sourced from pigs and highly processed. Other stabilizers include the sweetener sorbitol and the sugar molecules sucrose and lactose.
Polysorbate 80 is an emulsifier used in the food industry in ice creams, gelatin desserts, barbecue sauce, and pickled products. In vaccines, it helps other components remain soluble.
Some people have voiced concerns over the safety of polysorbate 80 after research showed potential links to reproductive problems in female rats and premature ovarian failure in girls receiving the quadrivalent human papillomavirus vaccine.
However, other scientists found no adverse effects when polysorbate 80 was included in a pneumococcal vaccine.
A group of experts from the Excipients Drafting Group at the European Medicines Agency has provisionally categorized polysorbate exposure from vaccines as "very low," below the threshold where it may cause toxicity.
Remnants of the vaccine production process
Vaccine manufacturers need sufficient quantities of bacteria and viruses to make the required doses.
Bacteria or viruses are often grown in large numbers before undergoing purification and then attenuation or inactivation during the production process.
Although most of the materials used during this expansion phase will be present in trace amounts or not at all in the final product, they may feature on the list of ingredients.
Antibiotics are used in the production of vaccines against some viruses to prevent bacterial contamination. The most commonly used antibiotics are neomycin, streptomycin, polymyxin B, gentamicin, and kanamycin.
Acidity regulators, such as succinic acid and disodium adipate, help keep the pH at the correct level during the expansion process.
Bovine serum is a component in some growth media formulations.
Ovalbumin is a protein in the whites of chicken eggs. The viral particles used in some flu and rabies vaccines are grown on chicken eggs, making it possible that small traces of ovalbumin will appear in the final product.
Glutaraldehyde and formaldehyde are chemicals used to inactivate toxins from viruses and bacteria in some vaccines. These chemicals are toxic in large quantities.
According to the Vaccine Knowledge Project at the University of Oxford in the United Kingdom, "a pear contains around 50 times more formaldehyde than is found in any vaccine."
Do vaccines contain human cell material?
Some vaccines are made from viruses or pathogenic molecules that are expanded in human, animal, or yeast cells.
There are two human cell lines that pharmaceutical companies use. These are called WI-38 and MRC-5. Both of these cell lines were established from cells taken from the lungs of aborted fetuses.
After expansion, viruses are harvested from these cell lines and purified. The chance of any human cell material being present in the vaccine is very small.
For some people, the fact that cells from aborted fetuses are used in this way presents a moral problem.
Other viruses are grown in animal cells before being incorporated into vaccines. Animal cells used for this purpose include kidney cells from African green monkeys (Vero cells) and chick embryo cells.
Some recombinant vaccines may contain small trace amounts of yeast proteins or yeast DNA.
Excipients in pharmaceuticals
While some people may be surprised to see excipients in vaccines, these compounds actually feature heavily in all medicines.
Sugars and flavoring in syrups mask the potentially unpleasant taste of the formulation, while colors help people avoid mistaking one drug for another. Some excipients improve how well a drug can penetrate the skin or determine where in the gastrointestinal tract its breakdown occurs.
As with vaccines, their purpose is to ensure that drugs are safe and effective.
The WHO estimate that vaccinations prevent between 2 and 3 million deaths every year across the globe. Severe side effects are very rare, making vaccines one of the safest healthcare interventions in the history of modern medicine.