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
Adjuvants are ingredients added to vaccines to enhance their response and create a stronger immune response in the patient’s body. Aluminum has been used as an adjuvant since the 1930s in the United States [1]. There are few side effects with aluminum, and it was the only adjuvant used in the U.S. for 70 years. Aluminum activates NALP3 inflammasome, which activates release of cytokine IL-1β. According to Casella & Mitchell, aluminum promotes predominantly a TH2-type antibody responses, which we now know is best suited for responses against extracellular pathogens and parasites [2]. Scientists have been looking for other adjuvants that may promote TH1 responses and better immune responses in general.
Recently, the FDA has approved new adjuvants. In Dr. Tapping’s lecture, one of the slides mentioned aluminum is the only adjuvant approved for use in the United States as opposed to places like Europe. However, according to the CDC website, new adjuvants like monophosphoryl lipid A and MF59 have been approved for use in a few vaccines [1]. Monophosphoryl lipid A has been used since 2009 in Cervarix, the vaccine used against HPV. Flaud is a new flu vaccine that contains MF59. MF59 is an oil-based adjuvant that boosts the immune response to this flu vaccine. Additionally, one licensed vaccine against H5N1 influenza contains AS03, but it is not available to the general public yet. AS03 is also an oil-based adjuvant [3].
Many scientists are excited about the prospects of using monophosphoryl lipid A (MPLA) as an adjuvant in vaccines. MPLA is derived from the lipopolysaccharide fraction of the cell walls of gram-negative bacteria, which boosts immunity via TLR4 [2]. More info about its low toxicity and mechanism as a TLR4 agonist is in [2].
[1] http://www.cdc.gov/vaccinesafety/concerns/adjuvants.html
[2] https://www.ncbi.nlm.nih.gov/pubmed/?term=Putting+endotoxin+to+work+for+us%3A+Monophosphoryl+lipid+A+as+a+safe+and+effective+vaccine+adjuvant
[3] http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm187810.htm
Great post and update on vaccine adjuvants. I obviously need to update that slide. There is much promise in new adjuvants for increasing vaccine safety and efficacy.
As future physicians, I know we're welcoming of more recent FDA-approved adjuvants but I wonder how a layperson would take the information, particularly those who are vaccination hesitant individuals? Having more effective vaccines is always a welcome advancement but administering them, nevertheless persuading patients of their safety, is another issue that we must tackle in order to achieve herd immunity.
Great job finding more information about the new adjuvants that the CDC has been looking into. I checked out the resource you used and found it helpful to answer a variety of questions. I am curious how oil based adjuvants could help specifically to boost the immune system for the flu vaccine.
Future Dr. Kim, thank you for contributing with your brilliant post on adjuvants! I was struck by your comment that aluminum has been utilized as an adjuvant for over 70 years. Is there any particular medical or economic reason for this fact? Or has research in other adjuvants proven to show less efficacy for triggered responses? I know you mentioned monophosphoryl lipid A and MF59 as newer adjuvants. Perhaps more trials and research with these adjuvants will show their efficacy in the near future!
@Angelina I am also excited to hear that the FDA is finally allowing the use of more adjuvants. MPLA is a more natural approach to boosting the immune response because it is a PAMP found in many bacterium cell walls. This should lead to less worry of adverse effects and have a lower toxicity than aluminum.
Very encouraging to hear that more adjuvants have been recently FDA approved! I imagine that modifications to increase the strength of the immune response will have a very positive impact on the efficacy of vaccines while minimizing their toxicity. Hopefully this will also help parents feel less reticent about getting their children vaccinated!