Types of Vaccine Ingredients
People often have questions about what ingredients are in vaccines and why. The ingredients can be described in five groups: antigens, adjuvants, stabilizers, preservatives and manufacturing byproducts. However, when thinking about vaccine ingredients, it can also be useful to think about the relative amounts of ingredients because as stated by Paracelsus, a 16th century physician and alchemist, “the dose makes the poison.”
Amounts of ingredients
The quote from Paracelsus is a good reminder that the quantity of an ingredient is equally important to what the ingredient is. For example, while we all know we need water to survive, too much water can be harmful. It may be tempting to dismiss this idea and instead try to avoid any exposure to an ingredient that is considered potentially harmful, but that approach is difficult to achieve because we live in a world made of chemicals.
If we only think about exposure from a vaccine while excluding other sources of exposure, it can skew our sense of risk. Opting out of vaccines because of concerns about the quantity of a particular ingredient may not change a person’s overall exposure to the ingredient, but it would leave them vulnerable to the diseases that those vaccine protect against. In short, vaccines — and the ingredients in them — are part of a much larger picture that we need to consider.
On some of the pages that follow in this section, we provide the quantities of ingredients in different vaccines, so we wanted to offer a brief refresher on some of the math and chemistry terminology that you may not have thought about since high school.
How much is 1 gram?
One gram is equal to:
- One-fifth (1/5) of a teaspoon of water
- One raisin
- One thousand (1,000) milligrams (Milligrams are often abbreviated as “mg.”)
- One million (1,000,000) micrograms (Micrograms are often abbreviated as “mcg” or “μg.”)
- One billion (1,000,000,000) nanograms (Nanograms are often abbreviated as “ng.”)
What does this mean when we talk about vaccines?
Vaccines do not contain grams of any ingredient. Most often they contain milligrams, micrograms or nanograms, so when reviewing quantities of ingredients, a useful tip for picturing these amounts is to think about a raisin:
- Milligram: A raisin would need to be cut into one thousand (1,000) equally sized pieces, and one of those pieces would be a milligram.
- Microgram: A raisin would need to be cut into one million (1,000,000) equally sized pieces, and one of those pieces would be a microgram.
- Nanogram: A raisin would need to be cut into one billion (1,000,000,000) equally sized pieces, and one of those pieces would be a nanogram.
If this still seems like “a lot,” try cutting a raisin into even 10 equally sized pieces, and you will quickly realize that we are talking about very small quantities.
What do “parts per million” and “parts per billion” mean?
Sometimes, you may see a quantity described as “parts per million” or “parts per billion.” These are abbreviated as “ppm” and “ppb,” respectively.
This labeling tells us how the quantities in a solution were measured. Rather than measuring the weight of the ingredient, its ratio in the solution was measured:
- 1 ppm means if the solution was divided into 1 million equal parts, one of those parts would be the ingredient, and the other 999,999 would be other types of ingredients.
- 1 ppb means if the solution was divided into 1 billion equal parts, one of those parts would be the ingredient, and the other 999,999,999 would be other types of ingredients.
A good rule of thumb is to remember that 1 ppm means about 1 mg of the chemical is present in 1 liter of water, so if a vaccine dose is 0.5 milliliters (ml):
- 1 ppm would be about 0.0005 milligrams in the dose.
- 1 ppb would be about 0.0000005 milligrams in the dose.
Antigens
Our immune systems respond to the part of the vaccine called the antigen. To be protected against potential disease-causing agents, the immune system needs to recognize specific parts of it. For this reason, vaccines will always contain something specific to the virus or bacteria they are designed to protect against.
The antigens in vaccines can be:
- Whole viruses or bacteria
- Parts of viruses or bacteria
- Harmful proteins, called toxins, made by bacteria
- Nucleic acids (e.g., mRNA or DNA) that cause our cells to make part of the virus or bacteria
The antigens in vaccines are designed so that they cannot cause the severe illness that can occur during an infection. Even if whole viruses or bacteria are used, they cannot cause severe illness like an infection would. When whole viruses or bacteria are used, one of two approaches may be taken:
- The viruses or bacteria are killed with chemicals so they can’t reproduce in the person
- The viruses or bacteria are changed in some way so that they only replicate a few times compared to the natural pathogen.
Learn more about how vaccines are made.
Adjuvants
Adjuvants are substances that make vaccines work better. They do this in one of three ways:
- Enhance the immune response to the vaccine
- Decrease the quantity of antigen needed
- Lessen the number of doses needed
Five types of adjuvants are approved for use in the U.S.:
- Aluminum salts — Salts that contain aluminum have been used in vaccines for about 100 years. Find out which vaccines contain aluminum, how much is present, and how we know aluminum in vaccines is safe.
- Monophosphoryl lipid A — This substance was isolated from the surface of bacteria. It has been changed so that it is not harmful when added to vaccines. The vaccines in the U.S. that currently use this adjuvant are the shingles vaccine (called Shingrix), one of the RSV vaccines (called Arexvy), and the protein-based COVID-19 vaccine (Nuvaxovid).
- QS21— This soap-based substance comes from the bark of Quillaja saponaria trees. It is used in the same vaccines that use monophosphoryl A. Those include the shingles vaccine (called Shingrix), one of the RSV vaccines (called Arexvy), and the protein-based COVID-19 vaccine (Nuvaxovid).
- MF59 — A substance composed of squalene oil mixed with water. Squalene is found in people, animals and plants. It is used in the U.S. in a version of the influenza vaccine (called FLUAD). Because squalene is an oil that can be found in plants, some people wonder whether they can get vaccines that contain MF59 if they have allergies to peanut or corn oils. The answer is yes because the squalene oil used in vaccines does not contain these oils.
- CpG — The C in this name stands for Cytosine, and the G stands for Guanine (G). They are connected by phosphate, which is represented by the lowercase p. Cytosine and Guanine are building blocks of DNA. When used as an adjuvant these two building blocks are linked together and added to the vaccine. One hepatitis B vaccine (called Heplisav-B) uses this adjuvant.
Stabilizers
Stabilizers protect vaccines during manufacture, storage and transport so that they work as expected when administered. Stabilizers can include salts, sugars or fats.
We offer webpages about two stabilizers that people sometimes have questions about:
- Gelatin – This stabilizer can be associated with allergic responses.
- Polysorbate 80 – This stabilizer can also be present in very low quantities as a manufacturing byproduct.
You can find other examples of stabilizers in the “ingredients by vaccine” section of our website.
Preservatives
Preservatives prevent bacterial or fungal contamination of vaccines. The need for preservatives in vaccines arose in the early 20th century. After getting vaccines contained in multi-dose vials, some children developed severe and occasionally deadly infections. Healthcare providers realized that sometimes when putting a needle in the top of the vial to draw up a dose of vaccine, contaminants would accidentally be introduced into the vial. When this happened, the person who got the current dose was fine, but the person who got the next dose would also be inoculated with the contaminant. If sufficient quantities of the contaminant were present to cause harm, the person could get sick.
In 1916, a typhoid vaccine contaminated with a bacteria, called Staphylococcus aureus, caused:
- 4 children to die
- 26 to develop local sores, called abscesses
- 68 to develop severe infections that spread throughout their bodies
Preservatives prevent these inadvertent contaminants. As a consequence of these types of incidents in the early 1900s, preservatives have been required for most vaccines contained in multi-dose vials since the 1930s.
In the U.S. today, many vaccines are sold in single dose vials, making preservatives less necessary. However, single dose vials increase the cost of vaccines, so in many developing countries multi-dose vials continue to be used, making preservatives important in those settings.
Thimerosal
Thimerosal is a mercury-containing preservative used for decades in vaccines. Because it contains mercury, thimerosal has been the focus of intense scrutiny. Thimerosal was removed from most routinely used childhood vaccines in the U.S. in the late 1990s. This is one of the reasons that the U.S. relies heavily on single-dose vaccine vials. However, thimerosal continues to be used in vaccines distributed in multi-dose vials in some other countries.
Because of fears that thimerosal contained in vaccines could harm children, several studies have evaluated its safety when used in childhood vaccines. Several separate, large, controlled studies found no evidence of harm. To find out more about thimerosal, its history and some of the safety studies, check our thimerosal webpage.
Manufacturing byproducts
Vaccines are different from medicines because they contain part of the virus or bacteria. This means vaccines are made differently than medicines. To grow viruses, cells must be used. For bacteria to replicate, nutrients must be present.
Once the antigen for a vaccine is produced, it is purified to remove the cells or nutrients used to make it. Purification processes have improved over time, but that doesn’t mean every last bit is gone. Think of the sand you bring back from the beach — no matter how much you try to get rid of it, some sand still ends up in your car or house. In the same way, small amounts of the nutrients and cell byproducts may remain in a vaccine. These amounts are so small that they cannot cause harm, but they are often still included on the vaccine ingredients list so that people are aware of their presence.
We offer details about several manufacturing byproducts, including:
Concerns have also been voiced about SV40, which is a virus found in cells used to grow the poliovirus vaccine during the 1950s and 1960s. These concerns were proven to be unfounded because children who received those vaccines were not at greater risk of cancer than those who didn’t receive them, and SV40 is not present in any of today’s vaccines. More information about SV40 is also contained on a separate webpage.
References
Adjuvants other than aluminum in vaccines
For a list of studies related to aluminum in vaccines, visit the aluminum page.
Squalene (MF59, AS03, AF03)
Weibel D, Sturkenboom M, Black, S, et al. Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines — multi-country assessment. Vaccine 2018; 38:6202.
The authors found no increased risk of narcolepsy in children or adults in Argentina, Canada, Spain, Switzerland, Taiwan and the Netherlands following implementation of squalene-adjuvanted (AS03, MF59) influenza H1N1 vaccines in those countries.
Dos Santos G, Seifert HA, Bauchau V, Shinde V, Barbeau DM, et al. Adjuvanted (AS03) A/H1N1 2009 Pandemic influenza vaccines and solid organ transplant rejection: systematic signal evaluation and lessons learnt. Drug Saf 2017;40:693-702.
In 2010, the European Medicines Agency (EMA) requested an assessment of available data following a signal of solid organ transplant (SOT) rejection after immunization with either of GlaxoSmithKline’s (GSK) two adjuvanted (AS03) pandemic influenza vaccines, Pandemrix and Arepanrix H1N1. The authors investigated 5,000 patients who received the 2009 A/H1N1 pandemic vaccine and an additional 11,000 subjects who received adjuvanted (AS03) A/H5N1 vaccines. They found that data supported the safety of adjuvanted (AS03) pandemic influenza vaccination in SOT recipients.
Kumar D, Campbell P, Hoschler K, Hildago L, Al-Dabbagh M, et al. Randomized controlled trial of adjuvanted versus non adjuvanted influenza vaccine in kidney transplant patients. Transplantation 2016;100;662-669.
The authors compared the safety and immunogenicity of the 2012-2013 influenza vaccine with or without MF59 adjuvant in adult patients who had received a kidney transplant within a median time of 8.1 years. They found no significant differences in response to the vaccine between groups and no evidence of HLA upregulation in transplant recipients who received adjuvanted vaccine.
Stassijns J, Bollaerts K, Baay M, Verstraeten T. A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children. Vaccine 2016; 34:714-722.
The authors conducted a systematic review on the safety of newly adjuvanted vaccines in more than 25,000 children ≤ 10 years of age, specifically those containing AS01, AS02, AS03 and MF59. They found that serious adverse events did not occur more frequently in the groups receiving adjuvanted vaccines.
Vesikari T, Forsten A, Arora A, Tsai T, Clemens R. Influenza vaccination in children primed with MF59-adjuvanted or non-adjuvanted seasonal influenza vaccine. Hum Vaccin Immunother 2015;11(8):2102-2112.
The authors compared the safety and immunogenicity of vaccination with trivalent inactivated influenza vaccine (TIV) versus MF59-adjuvanted TIV (aTIV) in children. They found that aTIV produced a significantly more robust immune response and a slightly higher but acceptable local and systemic reactions compared with TIV.
Rubinstein F, Micone P, Bonotti A, Wainer V, Schwarcz A, et al. Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicenter study. BMJ 2013;346:f393.
Approximately 30,000 pregnant women, including more than 7,000 vaccinated during pregnancy, and their newborns were evaluated to assess the risk of adverse perinatal events (fetal and maternal) associated with receipt of MF59-adjuvanted influenza vaccine. Vaccinated women had a significantly lower risk of preterm birth (< 37 weeks), low birth weight, early neonatal mortality, perinatal mortality (early neonatal mortality plus fetal mortality), low APGAR scores, infant non-immune jaundice, hospital admission during pregnancy, and first trimester hemorrhage compared with women who were not vaccinated during pregnancy.
Siegrist CA, Ambrosioni J, Bel M, Combescure C, Hadaya K, et al. Responses of solid organ transplant recipients to the AS03-adjuvanted pandemic influenza vaccine. Antivir Ther 2012;17(5):893-903.
During the 2009 H1N1 pandemic, solid organ transplant (SOT) recipients in Switzerland received two doses of an AS03-adjuvanted influenza vaccine (Pandemrix). The authors compared the safety and immunogenicity of two doses of AS03-adjuvanted vaccine in more than 200 SOT recipients (heart, lung, liver, kidney, pancreas/islet of Langerhans) to one dose in healthy family controls. Adverse reactions occurred less frequently in the SOT group and SOT graft function remained unaffected.
Black S, Della Cioppa G, Malfroot A, Nacci P, Nicolay U, et al. Safety of MF59-adjuvanted versus non-adjuvanted influenza vaccines in children and adolescents: an integrated analysis. Vaccine 2010;28:7331-7336.
The authors investigated the safety profile of MF59-adjuvanted and non-adjuvanted seasonal and pandemic influenza vaccines in more than 1,700 subjects aged 6 months to 18 years. Subjects in the MF59-adjuvanted group experienced a higher percentage of local and systemic reactions, such as injection site reactions or irritability. The group receiving adjuvanted influenza vaccines did not experience an increase in the incidence of serious adverse events.
Pellegrini M, Nicolay U, Lindert K, Groth N, Della Cioppa G. MF59-adjuvanted versus non-adjuvanted influenza vaccines: integrated analysis from a large safety database. Vaccine 2009;27:6959-6965.
The authors evaluated safety data from 64 clinical trials involving 20,000 recipients of MF59-containing seasonal and pandemic influenza vaccines. Other than an increased risk of local and systemic reactions such as injection site reactions or irritability, vaccine recipients had a lower risk of cardiovascular events, new onset chronic diseases, or death.
Monophosphoryl lipid A (MPL), saponin (QS21), and related adjuvant systems (AS01, AS02, AS04)
Bigaeva E, van Doorn E, Liu H, Hak E. Meta-analysis on randomized controlled trials of vaccines with QS-21 or ISCOMATRIX adjuvant: safety and tolerability. PLoSONE 2016;11(5):e0154757.
Saponin is an immunostimulant that is extracted from the bark of a South American tree, Quillaja sapnonaria. Two saponin-based adjuvants are QS21 and ISCOMATRIX. The authors conducted a systematic literature review to assess the safety and tolerability of saponin-based adjuvants and found no increase in the incidence of reported systemic adverse events.
Leroux-Roels G, Leroux-Roels I, Clement F, Ofori-Anyinam O, Lievens M, et al. Evaluation of the immune response to RTS,S/AS01 and RT,S/AS02 adjuvanted vaccines. Hum Vacc Immunother 2014;10(8):2211-2219.
The authors compared the safety and immunogenicity of malaria vaccines adjuvanted with squalene, monophosphoryl lipid A and saponin to a non-adjuvanted malaria vaccine in adults and found greater immune responses with adjuvanted vaccines. Adjuvanted vaccines had a higher rate of injection site reactions and certain generalized reactions (e.g., fatigue, headache) compared with the non-adjuvanted vaccine but within acceptable limits. These side effects typically resolved within seven days. No serious adverse events were reported for any group.
Toft L, Storgaard M, Muller M, Sehr P, Bonde P, et al. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J Infect Dis 2014;209:1165-1173.
The immune response and safety of Cervarix, a monophosphoryl lipid A-containing-HPV vaccine with Gardasil, an aluminum-adjuvanted HPV vaccine were compared in HIV infected adults. The authors found that Cervarix induced superior vaccine responses in HIV-infected women. Both vaccines were well tolerated, though Cervarix was associated with a higher rate of injection site reactions. No serious adverse events occurred in either group.
Wald A, Koelle DM, Fife K, Warren T, Leclair K, et al. Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons. Vaccine 2011;29(47):8520-8529.
A candidate vaccine, HerpV, against herpes simplex virus-2 (HSV-2) was tested for safety and immunogenicity in a phase 1 human adult study. The authors compared HerpV + QS21 (saponin adjuvant), HerpV alone, QS-21 alone and placebo. The vaccine was well tolerated and safe, and adverse events were similar between HerpV and HerpV + QS-21 groups.
Einstein MH, Baron M, Levin MJ, Chatterjee A, Edwards RP, et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) vaccines in healthy women aged 18-45 years. Hum Vaccin 2009;5(10):705-719.
The authors compared the immune response and safety of Cervarix, a monophosphoryl lipid A-containing- HPV vaccine with Gardasil, an aluminum-adjuvanted HPV vaccine in healthy adult women. They found that both vaccines were well tolerated, though Cervarixwas associated with a higher rate of injection site reactions, fatigue and myalgia, which were transient and resolved spontaneously without sequelae.
Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, et al. Analysis of adverse events of potential autoimmune aetiology in a large integrated database of AS04 adjuvanted vaccines. Vaccine 2008;26:6630-6638.
The authors assessed the safety of a monophosphoryl lipid A (MPL) containing adjuvant (AS04) in several vaccines (HPV 16/18, HBV, and phase 3 HSV). More than 68,000 patients were evaluated, including more than 39,000 who received HPV-16/18. The authors found a low rate of autoimmune disorders, without evidence of an increased risk associated with ASO4-adjuvanted vaccines versus non-adjuvanted vaccines.
Tong N, Beran J, Kee S, Miguel J, Sanchez C, et al. Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int 2005;68:2298-2303.
The authors compared the immunogenicity and safety of an AS04-adjuvanted hepatitis B vaccine with a non-adjuvanted hepatitis B vaccine and found the AS04-adjuvanted vaccine produced a more rapid onset and greater overall level of protection, necessitating fewer booster doses. The adjuvanted vaccine was associated with more injection site reactions, but the rates of serious adverse events were similar between groups, with all events determined to be unrelated to vaccination.
CpG
Hyer R, McGuire DK, Xing B, Jackson S, Janssen R. Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults. Vaccine 2018;36:2604-2611.
The authors describe the safety aspects of three trials comparing a CpG-ODN adjuvanted hepatitis B vaccine with an aluminum-adjuvanted hepatitis B vaccine in more than 13,000 adult subjects. Vaccine–associated adverse events were limited to mild to moderate local and systemic post-injection reactions. The authors found no differences in immune-mediated adverse events between the two groups.
Cooper CL, Davis HL, Morris ML, Efler SM, Kreig AM, et al. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine 2004;22:3136-3143.
CPG 7909, a CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immune response of a trivalent influenza vaccine. The authors compared Fluarix (full or 1/10th dose) plus CPG 7909 to Fluarix (full or 1/10th dose) plus saline and found all vaccines were generally well tolerated.
Stabilizers in vaccines
Gadzinowski J, Tansey SP, Wysocki J, et al. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine manufactured with and without polysorbate 80 given to healthy infants at 2, 3, 4, and 12 months of age. Pediatr Infect Dis J 2015;34:180-185.
The authors investigated the safety and immunogenicity of PCV-13 manufactured with or without polysorbate 80 (P80) in infants at 2, 3, 4 and 12 months of age. Immunogenicity and safety was similar for both formulations.
Preservatives in vaccines
For a list of studies related to thimerosal (mercury) in vaccines, visit the thimerosal page.
Reviewed by Paul A. Offit, MD, on May 19, 2026