Vaccines contain substances called antigens that enhance immunity, as well as a small amount of adjuvants, stabilizers, and preservatives that play a role in making the vaccine safe and effective. The biggest additive in vaccines is water. While the vaccine and other additives do not exceed a few milligrams, the water contribution is measured in grams. Vaccine volume is directly related to the way the vaccine is administered orally, nasally, or by injection.

Vaccine Content 

Vaccines contain substances called antigens that enhance immunity, as well as a small amount of adjuvants, stabilizers, and preservatives that play a role in making the vaccine safe and effective. The biggest additive in vaccines is water. While the vaccine and other additives do not exceed a few milligrams, the water contribution is measured in grams. Vaccine volume is directly related to the way the vaccine is administered orally, nasally, or by injection.



While some of the vaccine additives are used during the production phase, they may not remain in the product offered for use or may remain in trace amounts. It should also be kept in mind that most of the additives in the finished product are present in the human body in small or large amounts or are taken through different foods. Although it is necessary to evaluate each component separately, vaccine additives are available in very low amounts, safety tests are carried out in detail to ensure that they are not harmful to the human body, except for allergic reactions.

Active component 

It is a vaccine antigen. It occupies a few milligrams of space in the vaccine. It is the main active ingredient of the vaccine. It is a modified or partial form of the virus, bacteria, or toxin that causes the disease. It is no longer disease-causing. Some types of vaccines may use recombinant DNA technology or newer technologies.

Types of antigens that make up the active component of the vaccine:

  1. Live, Attenuated Viruses: Obtained by weakening wild-type or natural virus by different methods. When applied to the body, it does not cause disease, but an immune response develops. Immunity is provided with 1-2 doses of vaccine.
  2. Inactivated Viruses: The virus or a part of it is killed by chemicals such as formaldehyde, preventing it from multiplying by itself and causing disease. When the immune system encounters this virus again, it creates a response, but it requires multiple doses of vaccine.
  3. Part of the virus or bacteria: In vaccines such as hepatitis B, HPV, HiB, the immune system is stimulated by using a part of the virus. This virus fragment can be a surface protein or a polysaccharide.
  4. Part produced from bacteria: Bacterial toxins that are chemically inactivated and called toxoids are used in vaccine production. It has a disease-causing effect, albeit at a very low level.

Adjuvants 

They are auxiliary substances that are not immunogenic, do not form antibodies, but increase and strengthen the immunogenicity of the antigen to which they are administered. In this way, both the number of vaccinations and the cost are reduced.



The adjuvants were discovered by French veterinarian Gaston Ramon when he saw that the abscess, which is more common in horses than other animals, is reduced by adding some substances while producing diphtheria tetanus antiserum. In the same period, with the discovery that aluminum salts increase immunity, aluminum was used as the first adjuvant in 1932 and remained the only adjuvant used for about 70 years. Diphtheria, tetanus, pertussis, hepatitis A, hepatitis B, conjugated meningococcal, KPA, influenza, HPV vaccines currently produced contain adjuvant.

Aluminum, which has been used in millions of vaccines since 1932, acts as an adjuvant in different formulations such as aluminum potassium sulfate (AlK(SO4)2), aluminum hydroxide (Al(OH)3), aluminum phosphate (Al(PO4)3). In addition to its great contribution to reducing mortality and morbidity in vaccine-preventable diseases, it has minimal toxic effects. It is ineffective in vaccines that require T1 cell activity. For example, aluminum hydroxide is used as an adjuvant to make vaccines more effective at very low doses. The total amount of aluminum in all vaccines administered to a person throughout his life is 4.25 mg, which is at a very low level as determined by WHO and not harmful to human health. On the other hand, aluminum is abundant in drinking water, instant water, bakery products, medicines, especially stomach medicines, fruits and vegetables.

There are some studies showing that aluminum used as an adjuvant may have a neurotoxic effect. These studies claim that the adjuvant mechanism of action of aluminum is not well known, and that it may carry a risk for autoimmunity, encephalitis and associated neurological complications. However, many studies have found no evidence of neurotoxicity and other long-term side effects of aluminum-containing vaccines. Aluminum formulations can be used safely as adjuvant in vaccines in appropriate amounts.

The basic approach in modern adjuvant development studies is to develop or strengthen existing molecules or formulations that will minimize vaccine-induced adverse events and increase immune response without compromising safety. In this context, various adjuvants such as AS04, AS03, MF59 and Virosome have been used.

Protectors 

The preservatives, which were started to be used to prevent bacterial contamination in multi-dose vaccines, but were added to many vaccines later on, are added to prevent bacterial and fungal infections and to protect the vaccine content. However, it does not completely eliminate the risk of contamination. For this purpose, mostly thiomersal, phenoxyethanol and phenol are used.



Phenoxyethanol is an aromatic ether alcohol and is also used as a preservative in many products in the cosmetic industry. There are no reported side effects other than eczema. It is used to inactivate viruses (eg IPV) and to detoxify bacterial toxins in diphtheria and tetanus vaccines. Formaldehyde purification is carried out in vaccines during production. The amount of formaldehyde in vaccines is several hundred times lower than the amount known to harm humans, even infants. For example, the quintuple combination vaccine contains less than 0.02% or less than 200 parts per million formaldehyde per dose.

Phenol is an aromatic alcohol used in few vaccines.

Thiomersal is a very widely used preservative compound containing ethyl mercury. It has been subjected to intense criticism and scrutiny due to its mercury content, but no harmful effects have been reported with thiomersaline, which has been used since the 1930s, except for minor reactions (eg, redness, swelling at the injection site). It is used in many countries to prevent contamination, especially in multi-dose vials, as it helps to reduce storage requirements/costs. The period of removal of the ethyl mercury compound from the body is 7-10 days. The period of removal of methyl mercury, which is a toxic compound and abundant in seafood, is 50 days. Thiomersal does not contain methyl mercury. So far, there has been no evidence of toxicity when exposed to vaccine-derived thiomersal. However, vaccine hesitations due to the recent attempts to establish a relationship with autism or other neurological defects have led the industry to develop vaccines that do not contain thiomersal as a preservative.

Stabilizers 

It ensures that the vaccine remains active during transport and storage, preserves protein structures and regulates the osmolar concentration. Stabilizers are used to form a filler material when the vaccine is in very small quantities. Examples include magnesium chloride, polysorbate 80, sugars or gelatin. The choice of stabilizer is determined by the nature and nature of the active pharmaceutical ingredient or viral antigen(s) in the vaccine.



Gelatin used as a stabilizer in vaccines can be of vegetable or animal origin. Animal-derived gelatin obtained from chicken, cattle or pigs is included as an additive in many medicines. Gelatin is highly purified and hydrolyzed when used in vaccines. Some studies show that the DNA structure of the gelatin in the vaccine has changed too much compared to the animal DNA structure. However, pork-derived gelatin is of particular concern to some Jewish groups and Muslims. Although some religious opinion leaders state that porcine gelatin is not taken orally, so there is no situation contrary to their beliefs, these concerns appear as an important reason for vaccine rejection. For this reason, bovine gelatin is requested in the technical specifications of vaccine tenders in many Muslim countries. Pork gelatin is also used in some vaccines such as MMR and chickenpox in the world.

Other additives 

Other than preservatives, adjuvants and stabilizers, additives are residual amounts that have been used during the manufacturing process mainly to prevent microbiological contamination.

Cell culture materials 

Some materials, such as egg protein, various culture media, are used to amplify vaccine antigens.

Inactivating substances 

They are substances used to kill viruses or neutralize toxins. This prevents vaccines from causing disease. For example, formaldehyde is naturally found in the human body to generate energy and provide some essential materials such as amino acids, while the amount found in vaccines is far below this. Studies show that 50-70 times more of the amount of formaldehyde taken by a newborn baby with a dose of vaccine is naturally found in the baby’s body. It has been shown that the amount of formaldehyde, which acts as a carcinogen, is the amount taken from the air by respiration.

Antibiotics 

It is used to prevent bacterial contamination. Considering the antibiotics in some vaccines, neomycin, kanamycin, erythromycin, polymyxin B, streptomycin, chlortetracycline, amphotericin B are used, while penicillin, cephalosporin group antibiotics with a higher risk of allergic reaction are not used. The amount of antibiotics used is either trace or immeasurably low. Most antibiotic additives are destroyed by purification during the production phase of the vaccine, but traces may remain in a small number of vaccines.

 


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