From the Guidelines
Adjuvants in vaccines work by activating pattern recognition receptors, triggering an inflammatory response, and enhancing antigen uptake, ultimately leading to a stronger immune response, as seen with the MF59 adjuvant in influenza vaccines 1. The mechanism of action of adjuvants in vaccination involves several key steps:
- Creating a depot effect at the injection site, which prolongs antigen exposure to the immune system
- Activating pattern recognition receptors (PRRs) like Toll-like receptors on antigen-presenting cells
- Triggering the release of pro-inflammatory cytokines and chemokines, which recruits immune cells to the injection site
- Enhancing antigen uptake by dendritic cells, which then migrate to lymph nodes where they present antigens to T cells
- Enhancing co-stimulatory molecule expression on antigen-presenting cells, essential for effective T cell activation The use of adjuvants like MF59 in influenza vaccines has been shown to elicit a strong antigenic response without the need for a higher antigen dose, making them a valuable tool in vaccine development 1. Some common adjuvants include:
- Aluminum salts (alum), which adsorb antigens and create a depot effect
- Oil-in-water emulsions like MF59, which enhance antigen uptake
- TLR agonists such as monophosphoryl lipid A (MPL), which directly stimulate innate immune receptors By boosting both innate and adaptive immune responses, adjuvants allow for dose-sparing of precious antigens and help generate stronger, longer-lasting immunity, particularly important for inactivated vaccines and recombinant protein antigens 1.
From the Research
Mechanism of Action of Adjuvants in Vaccination
The mechanism of action of adjuvants in vaccination is complex and involves multiple pathways. Key aspects include:
- Controlling how the immune system is exposed to the immunogen and providing inflammatory cues that enable productive immune priming 2
- Enhancing the level and breadth of the immune response to a target antigen, thereby enhancing protection from the associated disease 3
- Categorization as immunostimulants and delivery systems, with immunostimulants leading to the maturation and activation of antigen-presenting cells (APCs) and delivery systems facilitating antigen presentation by prolonging the bioavailability of the loaded antigens 4
Adjuvant Mechanisms
Adjuvants may act by a combination of various mechanisms, including:
- Formation of depot
- Induction of cytokines and chemokines
- Recruitment of immune cells
- Enhancement of antigen uptake and presentation
- Promoting antigen transport to draining lymph nodes 5 These mechanisms activate innate immune responses to create a local immuno-competent environment at the injection site, altering the quality and quantity of adaptive immune responses.
Novel Adjuvant Approaches
Novel approaches to adjuvant design include conjugation of antigen and adjuvant, enabling the use of smaller amounts of adjuvant and avoiding unnecessary tissue damage and activation of bystander cells 6. This can ensure that all APCs that take up the antigen become activated, avoiding tolerogenesis and leading to a strong activation response in dendritic cells and macrophages.