What are common types of adjuvants used in vaccines?
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Executive summary
Adjuvants commonly used in licensed vaccines include aluminum salts (alum), oil‑in‑water emulsions such as MF59, saponin‑based complexes like QS21/Matrix‑M, toll‑like receptor (TLR) agonists such as monophosphoryl lipid A (MPL) and CpG oligonucleotides, and lipid‑based delivery systems (LNPs) that can act as adjuvants for mRNA vaccines [1] [2] [3] [4]. Regulatory and clinical sources emphasize aluminum salts remain the most widely used historically, while engineered adjuvant systems (e.g., AS01/AS04, MF59, Matrix‑M) and nucleic‑acid TLR agonists are increasingly used to shape stronger or Th1‑biased responses [1] [2] [3].
1. Aluminum salts — the longtime workhorse
Aluminum‑based adjuvants (aluminum hydroxide, aluminum phosphate and related salts) are the historically dominant class used in many routine vaccines (DTaP, Hib, hepatitis A/B, HPV, pneumococcal and meningococcal) and are still the most widely used worldwide [5] [6] [1]. Regulatory texts set maximum aluminum per dose (for example, the European Pharmacopeia allows up to 1.25 mg per dose in certain circumstances), and public health reporting notes most aluminum‑adjuvanted vaccines contain less than 0.5 mg per dose [7] [6].
2. Oil‑in‑water emulsions — MF59 and cousins
Emulsion adjuvants such as MF59 (a squalene oil‑in‑water formulation) enhance responses by creating local inflammation and antigen retention in lymphoid tissues; MF59 has been licensed in influenza vaccines in Europe since the 1990s and is used selectively in older adults in the U.S. [2] [3]. Reviews describe how MF59 promotes antigen deposition in lymph node macrophage compartments and can boost antibody magnitude and quality [3] [2].
3. Saponin complexes and nanoparticle systems — QS21 and Matrix‑M
Saponin‑derived adjuvants (QS21) and their formulated complexes (AS01 family, Matrix‑M) are used to produce potent cellular and humoral immunity; these appear in shingles (Shingrix) and some COVID‑19 and RSV vaccines, and Matrix‑M is a component in Novavax and other vaccines under regulatory review [8] [7] [9]. Clinical reviewers highlight saponin complexes’ ability to elicit strong T‑cell and antibody responses, which is why they are chosen for vaccines requiring robust cellular immunity [2] [9].
4. TLR agonists and nucleic‑acid adjuvants — MPL, CpG and other immune stimulators
Adjuvant systems increasingly include defined immunostimulants that target innate sensors. Monophosphoryl lipid A (MPL) — derived from bacterial lipopolysaccharide — is used in licensed vaccines (for example in AS04) to bias towards Th1 responses, while CpG oligonucleotides (synthetic DNA sequences that engage TLR9) directly activate B cells and plasmacytoid dendritic cells to promote Th1 and memory responses [8] [3] [2]. Recent reviews note a trend toward rationally designed adjuvant systems combining antigen delivery with TLR agonists to tailor immunity [1] [3].
5. Lipid nanoparticles and particulate delivery — dual role as carrier and adjuvant
Modern vaccine platforms (notably mRNA) use lipid nanoparticles (LNPs) that primarily act as delivery vehicles but also have intrinsic immune‑activating properties and therefore function as adjuvants in practice [4]. Surveyed literature groups adjuvants into immune enhancers, delivery systems and combination products — reflecting the growing overlap between formulation technology and immunostimulation [4].
6. How regulators and experts frame safety and choices
Regulatory bodies and public‑health reviewers emphasize both long experience with aluminum salts and careful, targeted use of newer adjuvants; safety and indication determine choice. Vaccines with modern adjuvant systems remain relatively few compared with alum‑containing products, but the landscape is shifting as immunology and molecular design enable more potent, tailored adjuvants [1] [2]. Public debate has focused recently on aluminum safety, with fact‑checking and CDC/academic sources disputing claims linking vaccine aluminum to autism or other chronic conditions [10] [6] [8].
7. Why different adjuvants matter — matching biology to the pathogen
Adjuvant selection is a deliberate trade‑off: aluminum salts reliably raise antibody titers for many protein antigens; emulsions and saponin complexes can increase breadth and cellular immunity; TLR agonists steer immunity toward Th1 and stronger memory; and particulate/lipid systems improve antigen delivery and innate sensing [5] [3] [4]. Reviews stress that highly purified antigen vaccines often require these engineered adjuvants to achieve protective efficacy [1] [9].
Limitations and next steps: available sources summarize common, licensed and investigational adjuvant classes but do not provide an exhaustive list of every experimental compound in development; for claims beyond what these reviews state, not found in current reporting.