Table Info

Table 1.

Examples of types of adjuvants, their mode of action and their key advantages and disadvantages

Adjuvant	Mode of action	Representative examples	Type of antigen	Advantages	Disadvantages
Mineral salts	Retain antigen at site of injection (short-term depot) and induce Th₂ responses	Aluminium hydroxide Aluminium phosphate Brands: Alhydrogel, Adjuphos, Imject Alum	Extracellular pathogens Live virus Inactivated virus	Good safety profile Low cost Strong humoral response	Multiple injections often necessary High reactogenicity in felines (abscess, sarcomas, and granulomas) Adsorption based on characteristics of antigen Does not induce Th₁ immunity Cannot be easily frozen or lyophilized
Oil emulsions	Form antigen depot at injection site and induce inflammatory cytokines	MF59 AS03 Emulsigen-D Montanide	Live virus Inactivated virus	Strong Th₂ immunity Low cost Long term immunity	Weak Th₁ response Scar tissue formation and adhesion Granuloma and cyst formation Inflammation, irritation and pain at injection site Reactogenicity (injection site reactions) Potential contamination from carcinogenic hydrocarbons
Immune-stimulating complexes (ISCOM)	Activate inflammasome, induce DNA release activate TLRs, induce T cell and humoral responses	Saponins Brands: Quil A, QS21, ISCOM, VetSap	Viral Bacterial Parasitic	Strong humoral and cellular immune response	Potential toxicity Haemolysis Granulomas Local inflammatory reactions Pain at injection site
Bacterial products and derivatives	Activate TLRs and elicit strong humoral and T cell responses	Monophosphoryl lipid A (MPL) Alum + MPL (AS04)	Protein Subunit	High antibody responses Mucosal or transcutaneous use	High reactogenicity (fever, arthritis, uveitis) Poor consistency between preparations Not cost-effective
Cytokines	Activate antigen presenting cells and provide co-stimulatory signals to B cells and T cells	Granulocyte-macrophage colony stimulating factor (GM-CSF)	Cancer	Good antitumor immunity	Limited application due to poor stability and toxicity High cost May promote autoimmunity
Particles (nano- and micro-)	Encapsulate antigen in biodegradable polymers, providing depot effect and targeting of antigen to antigen presenting cells	Poly(D,L-lactide-co-glycolic acid) polymer ester (PLGA) Poly(lactic acid) (PLA) Chitosan Polyphosphazenes	Recombinant protein DNA	Controlled release of antigen Reduced inflammatory response Biodegradable and biocompatible	Antigen release rate influenced by type of microparticle. Dosage may be difficult to optimise Antigen stability issues during production and storage
TLR ligands	Engage TLRs leading to cytokine expression and Th₁ activity	Poly I:C CpG MPLA	Viral Bacterial Parasitic Protein	Can stimulate Th₁ immunity and mucosal immunity Small size Good stability	High doses may result in splenomegaly Can trigger cytokine release syndrome
Polysaccharides	Stimulate both cellular and humoral immunity via DC-SIGN activation and activate complement pathway	Delta inulin (Advax^®)	Viral Bacterial Parasitic Toxin Recombinant protein	Does not require adsorption of antigen Can be combined with other adjuvants	None identified
Combination adjuvants	Combination of immune stimulators with antigen delivery systems	Advax-CpG55.2 Alum + MPLA Alum + CpG	Viral Bacterial Parasitic Toxin Recombinant protein	Enhances both Th₁ and Th₂ immunity, thereby maximizing both neutralizing antibody as well as cellular immunity	See data on individual components

TLRs: Toll-like receptors

Declarations

Disclaimer

The viewpoint and content of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Author contributions

AA: Writing—original draft. NP: Conceptualisation, Supervision, Writing—review & editing.

Conflicts of interest

AA and NP are affiliated with Vaxine Pty Ltd which hold proprietary interests over Advax-CpG adjuvant.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Development of Advax-CpG55.2 adjuvant was supported by funding from National Institute of Allergy and Infectious Diseases of the National Institutes of Health [HHS-N272201400053C, HHSN272201800044C]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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