Adjuvants

Prepare an emulsion in the form of water-in-oil (W/O) or oil-in-water (O/W) by emulsifying a certain proportion of oil phase and water phase materials.

These adjuvants are mainly aluminum and magnesium salt compounds. Aluminum adjuvants were the first adjuvants approved for use in human vaccines. The two most commonly used aluminum-based adjuvants in licensed vaccines are aluminum hydroxide and aluminum phosphate. Aluminum adjuvants enhance the production of IgG1 and IgE antibodies by promoting Th2 cell responses.

Lipid A in lipopolysaccharide (LPS) is the primary inducer of inflammatory responses and possesses potent immunostimulatory effects; however, its toxicity limits its application as an immunological adjuvant or therapeutic agent. After hydrolyzing the main active component of LPS, lipid A, the monophosphorylated compound MPL is obtained. The toxicity of MPL is at most 0.08% of that of the parent LPS, while its immunomodulatory activity is largely, if not entirely, retained. MPL has been used as an adjuvant in seven vaccines.

CpG is a non-methylated cytosine-guanine oligonucleotide widely found in bacteria, viruses, and other non-vertebrate organisms. It can adsorb antigens through physical mixing and chemical coupling. CpG can mimic pathogen invasion and damage to living cells, transmitting danger signals to the innate immune system, thereby activating pathogen-associated molecular patterns (PAMPs) or DAMP recognized and mediated by pattern recognition receptors (PRRs), and activating innate immune cells.

Multiple saponins have been applied in vaccine adjuvants. Saponins possess a unique hemolytic effect that disrupts red blood cell membranes and have an auxiliary function in escaping endosomes. They are currently being developed for use in mRNA vaccines, ADC drugs, small nucleic acids, and other pharmaceuticals. AS01 is composed of two immunostimulants: MPLA and a lipid-based adjuvant derived from the triterpenoid glycoside (Quillaja saponaria 21, QS-21) purified from the bark extract of Quillaja saponaria Molina.

Bacteria, fungi, viruses, and certain components of plants can activate the innate immune system by targeting pattern recognition receptors, thereby becoming potential vaccine adjuvants. Toll-like receptors are transmembrane signaling molecules expressed on the surface of immune cells. The ligands that bind to them must be highly specific, and these ligands are pathogen-associated molecular patterns with distinct evolutionary characteristics.