Vaccine Ingredients—What Is All That Stuff Anyway?
All things are poison, and nothing is without poison. The dosage alone makes it so a thing is not a poison.
There’s little that worries vaccine-hesitant patients more than the “stuff” that is in vaccines. They have heard that vaccine ingredients are “toxic.” They have heard that there is aborted fetal tissue and that there are monkey cells in our vaccines. The substances listed in the package inserts often have long and unusual-sounding chemical names that are not easily recognizable. It is easy to see why vaccine ingredients could be concerning for some people. However, the reality of what’s in vaccines is much less frightening. Unlike lists of food ingredients, vaccine ingredients must include products used in the process of manufacturing a vaccine, even if none of that substance, or only trace amounts of that substance, remain in the final product. Moreover, many of the ingredients found in vaccines or used in production of vaccines actually already exist in the human body (for example, sodium, potassium, urea, histidine, and formaldehyde) or are in foods we consume every day (such as sucrose, dextrose, lactose, vitamins, yeast, and eggs).
This chapter will take you through the steps of vaccine production, highlighting the substances used along the way (known as excipients). In learning the process of making a vaccine and the purpose of the ingredients used in the manufacturing and final production of a vaccine, we can hopefully make that “stuff” that is in vaccines seem much less scary.
Let’s start from the beginning. First, the bacteria or viruses that we are using to build an immunity to through vaccination have to be grown and replicated.
Growth of Viruses and Bacteria. Viruses and bacteria are the active ingredients in a vaccine. Some vaccines contain whole viruses or bacteria that are either live but weakened, or are killed and fully inactivated. Other vaccines contain only pieces of viruses or bacteria (usually proteins or sugars from the surface of the organism), which trigger the immune response but do not cause disease.
1. Human and animal cells—Viruses will only grow in human or animal cells. Cells are the “manufacturing plants” for viruses and bacteria. Within the cells, these organisms can grow and replicate, later to be separated from their cellular “homes” and purified multiple times over. DNA is not stable when exposed to chemicals and is, therefore, denatured or broken down so much that exceedingly tiny amounts (on the order of trillions of a gram) of DNA, if any, remain in the final vaccine product. Any DNA that does remain is highly fragmented and could not create a whole protein. In such a state, it is practically impossible for any DNA from the vaccine manufacturing process to incorporate itself into the DNA of the person getting the vaccine. If this could occur, gene therapy would be much easier than it has turned out to be.1
Human cell strains—As discussed in chapter 10, there are two human cell lines (WI-38 and MRC-5) used in vaccine production.
Animal cell strains—A variety of animal cells are also used in viral vaccine production, including Vero cells (derived from cells of an African green monkey), embryonic chick and duck cells, Madin-Darby canine kidney cells (derived from cells of an adult cocker spaniel), insect cells, and embryonic guinea pig cells.2,3
Genetically modified organisms—Use of genetically modified cells or genetic material (DNA or RNA) within those cells is a promising method of vaccine production under study. A virus itself may be genetically altered, rendering it noninfectious but retaining the ability to stimulate an immune response. Or, DNA that codes a part of an infectious organism can be placed into another organism for mass production to later be used for vaccine manufacture.4
Recombinant DNA technology—This is a type of genetic modification technology. Recombinant vaccines are made when small pieces of DNA from the organism we want to protect against are put into bacterial or yeast cells to produce large quantities of an active ingredient for manufacture of the vaccine. In the case of the hepatitis B vaccine, for example, yeast cells are used to produce a hepatitis B surface protein.5
2. Growth media—Some bacteria do not need to be grown in human or animal cells but can instead be grown on cultures using nutrient-rich media to foster growth. There are numerous brands of growth media used in vaccine production, including, Eagle’s medium, Stainer-Scholte medium, Medium 199, and others.6 Media ingredients typically include proteins (for example, soy peptone and bovine casein), amino acids (for example, L-cysteine and L-histamine), vitamins (for example, ferric nitrate and magnesium sulfate), carbohydrates (for example, dextrose and galactose), and salts (for example, potassium chloride and sodium pyruvate). These and other ingredients are used at this stage of the production process to provide an optimal growth environment for the active vaccine ingredients.7
Next, the desirable viruses or bacteria or pieces of viruses or bacteria that are needed for vaccine production have to be processed and purified.
Processing and Purification. Substances used in production of vaccines may or may not have any residual presence in the finished product. If there is any substance remaining, it is usually only in trace amounts. The following are the various substances used in processing and purifying the vaccine.
1. Antibiotics: These are used only during manufacturing to prevent bacteria from growing in and contaminating the vaccine. Antibiotics that commonly cause allergic reactions (such as sulfa- and penicillin-containing antibiotics) are not used. Less commonly allergenic antibiotics (such as neomycin and polymyxin B) are used for production of vaccines. There may be tiny amounts of antibiotic remaining in the final vaccine product, but, depending on the type of allergic reaction, people with mild allergies could still receive vaccines that use the antibiotic in production. This should be discussed with a medical provider first, however.
2. Inactivating agents: These are used to inactivate viruses and bacteria so that they can’t induce the illness against which they are meant to protect. These agents are diluted significantly and very little remain in the final vaccine product. These include formaldehyde (a pear has 50 times more formaldehyde than any vaccine),5 glutaraldehyde (the amount remaining in any vaccine is <50 ng, which is one billionth of a gram),8 and beta-propriolactone (which is present only in the anthrax vaccine and, after placement in solution with water, is fully broken down and harmless).9
3. Protein purifiers: The purpose of protein purification is to separate out or isolate one or a few proteins of interest from a complex mixture of process-related impurities (such as those used in growing a virus or bacterium). The goal is to retain the largest amount of protein with the fewest amount of contaminants. Some of the substances used in the purification process include ammonium sulfate, cetyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, and sodium taurodeoxycholate.10
Then, the purified virus, bacterium, or particle has to be “packaged” in a solution for administration to patients.
Making the Final Product. Other than the virus or bacterium itself, the substances that make up the ultimate components of a vaccine are those that enhance immunogenicity (or ability to induce an immune response), allow the viral and bacterial proteins and other ingredients to remain in solution, and enable stability of the vaccine over time and across changes in temperature, acidity, light, and humidity.
1. Adjuvants—These are used to “strengthen and lengthen” the immune response to a vaccine. They also absorb protein that helps keep the vaccine components from sticking to the walls of the container during storage.5 They are only used in inactivated virus vaccines.
Aluminum: Aluminum hydroxide, aluminum phosphate, potassium aluminum phosphate, potassium aluminum sulfate, and amorphous aluminum hydroxyphosphate sulfate.
Also found in most naturally occurring foods, water, breast milk, formula, breads, cakes, antacids, food packaging products, and more
Vaccines with aluminum are more likely to cause redness and hardness at the injection site and rarely cause a granuloma (localized mass of granulation tissue), which is not dangerous but can last for months to years
MF59 (squalene oil): MF59 comes from highly purified fish oil. It is only used in Fluad, an influenza vaccine, which is used in people older than 65 years of age.
Also found in naturally occurring oil found in humans, plants, and animals
Common side effects related to MF59 are injection site pain, swelling, redness, low-grade temperature, headache, malaise, fatigue, and shivering5
MPL (3-O-desacyl-4’-monophosphoryl lipid A): This form of lipid A molecule induces a strong immune response but is 100-fold less toxic than other forms, such as lipopolysaccharide.11 It is currently only a component of the bivalent HPV vaccine, which is no longer commonly recommended, given availability of the nine-valent vaccine.
Xanthan: This is traditionally used as a thickening agent and stabilizer. It is present in the rotavirus diluent, but it is also being studied and holds promise as an adjuvant to improve the immune response to vaccines.12
Also found in toothpaste, medicines, gluten-free foods, yogurt, ice cream, and other commonly used products
QS-21: This compound is derived from the Chilean soapbark tree (Quillaja saponaria) and is used as an adjuvant in the Shingrix vaccine to enhance immune response. It is also under investigation for use in HIV, malaria, and cancer vaccines.13