Saar Kuzi
Alessandra Coutinho Fernandes
William Cope
Richard Tapping
Kashif Ahmad
Reda Sadki
Shubhra Kanti Karmaker Santu
Adam P Rusch
Elle Meisner
Nereyda Ochoa
Landon J. Kunzelman
James DotimasFA16 Immunization Module’s Updates
Adjuvants in Vaccine Formulations
An adjuvant is a substance that serves the function of being an immune system potentiator in vaccines. This is achieved by triggering an early response by the innate immune system. The desired innate immune responses that adjuvants induce are an inflammatory response as well as the activation of antigen-presenting cells (APCs). These activated APCs will then produce cytokines necessary for the activation and differentiation of T cells much more rapidly and in larger quantities than would otherwise occur.
Currently there are two adjuvants that are utilized in vaccines in the U.S. The first are aluminum salts which include aluminum hydroxide, aluminum phosphate, potassium aluminum sulfate, and mixed aluminum salts. These aluminum salts are used in DTAP, pneumococcal conjugate, Haemophihlus influenza type b, and hepatitis A and B vaccines. The other adjuvant that has been approved for use in the U.S. is monophosphoryl lipid A (MPL), a purified fat-like substance. MPL is used in the Cervarix vaccine that is administered to protect against the human papillomavirus types 16 and 18.
It should also be mentioned that not all vaccines contain or even require an adjuvant because many vaccines are able to elicit an adequate immune response without the presence of an artificial adjuvant due to the presence of naturally occurring immune potentiators naturally present within the vaccine. There are many types of adjuvants that have potential use, including: mineral salts, bacterial products, toxins, lipids, nucleic acids, peptidoglycans, carbohydrates, peptides, cytokines, hormones, and small organic molecules to name a few. Many of these are current subjects of adjuvant research. One being heavily researched are the small organic molecules due to their ability to act as Toll-like receptor (TLR) agonists. An example of this are various synthetic adenine derivatives which act as TLR7 agonists. These adenine derivatives can potentially play an important role in viral vaccines because they have been found to have interferon-inducing (IFN-inducing) activities. TLR7 plays an important role in the immune response to viruses because it recognizes single stranded RNA, small interfering RNA, as well as these adenine derivatives leading to IFN production.
References:
https://www.ncbi.nlm.nih.gov/pubmed/15812492
http://www.cdc.gov/vaccinesafety/concerns/adjuvants.html
http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm187810.htm
https://www.ncbi.nlm.nih.gov/pubmed/17275323
https://www.ncbi.nlm.nih.gov/pubmed/16539397
https://www.ncbi.nlm.nih.gov/pubmed/22481916
Based on your descriptions, it sounds like adjuvants are in general a great boon for vaccines. I can understand decisions for using adjuvants for vaccines with particularly weak responses, but I am curious about the threshold or conditions for ultimately using them in a vaccine. Behind the scenes, I can see how cost/benefit analyses might affect the decision (e.g: the cost of an adjuvant may not compensate for marginal increases in the intensity of an immune response). I wonder if there have been reasonable vaccines against certain diseases that have fell on the chopping table because of unreasonable production costs.
Hey Adam! This is a very interesting topic and it leads me to question if there are any side effects of administering these aluminum salts into the immune system. They seem to target very important pathways associated with the TLRs you mentioned and interferon inducing activities. I wonder if over- or under-administration of these salts could trigger our immune systems to react in a negative way. I did my update on the methods of storing vaccines, so I wonder if there are any guidelines for storing these salts as well. It seems that these artificial adjuvants must be kept in a very stable condition in order to maintain functionality once its administered. All in all pretty cool stuff!