Table 2.

Adjuvants in licensed human vaccines

Type	First licensed	Description	Adjuvant	Vaccine examples
Alum (aluminium salts)	1920	Suspension of phosphate and hydroxide salts. Adsorption of antigens forms depot effect. Activates NALP3 inflammasome	Aluminium phosphate	Diphtheria, pertussis, tetanus (e.g., Adacel) [92]
				Pneumococcus (e.g., Synflorix) [93]
				Neisseria meningitidis (e.g., Trumenba®) [94]
			Aluminium hydroxide	Anthrax (BioThrax®) [95]
				Hepatitis B (Engerix B) [96]
				Hepatitis A (e.g., Havrix®) [97]
				Japanese encephalitis (Ixiaro®) [98]
				Neisseria menigitis (e.g., Menjugate®) [97]
				Pneumococcus (e.g., Prevenar) [99]
			Aluminium phosphate and aluminium hydroxide	Diphtheria, pertussis, tetanus (e.g., Boostrix®) [100]
			Aluminium phosphate and amorphous aluminium hydroxyphosphate sulfate	Diphtheria, pertussis, tetanus (e.g., Vaxelis®) [101]
			Amorphous aluminium hydroxyphosphate sulfate	Human papilloma virus (e.g., Gardasil®) [102]
				Hepatitis B (e.g., Recombivax) [103]
Oil-in-water emulsion	1997	Stabilized squalene oil in water emulsion induces inflammatory cytokines and forms antigen depot	MF59 AS03	Influenza (e.g., Fluad®, Pandemrix®) [104]
Immune potentiator	2022	Alum + TLR7/8 agonist	Alhydroxyquim	COVID-19 (Covaxin®) [105]
	2004	Synthetic TLR4 ligand adsorbed to aluminum hydroxide	RC-529	Hepatitis B [106]
	2013	Naturally derived TLR4 ligand adsorbed onto L-tyrosine	Monophosphoryl lipid A (MPL)	Pollen allergy (Pollinex®) [107]
	2012	TLR9 agonist CpG oligonucleotide	ISS1018	Hepatitis B (Heplisav®) [66]
	2022	Increased cellular and humoral immunity	Alum-CpG1018	COVID-19 (CorbeVax®) [108]
Combined adjuvants	2017	Liposome co-delivering MPL and QS21	AS01B	Shingles (Shingrix®) [109]
				Malaria (Mosquirix®) [110]
	2005	MPL adsorbed on aluminium phosphate	AS04	Human papilloma virus (e.g., Cervarix™) [111]
				Hepatitis B (Fendrix®) [112]
	2021	Delta inulin with synthetic CpG oligonucleotide	Advax-CpG55.2™	COVID-19 (Spikogen®) [42]
Saponin complex	2021	Saponin mixed with cholesterol	Matrix-M	COVID-19 (Nuvaxovid™) [113]

TLR: Toll-like receptor