![]() ![]() 10 Subsequently, it was discovered that some delivery materials can also act as adjuvants by enhancing adaptive immune responses through mimicking the size or spatial structure of natural pathogens to facilitate antigen uptake and presentation by antigen-presenting cells (APCs). 9 Adjuvants guide and enhance specific adaptive immune responses by targeting innate immune cells and activating pattern recognition receptors (PRRs) signaling pathways. It was not until the revelation of the mechanism by which the innate immune response controls the adaptive immune response that scientists began to understand the action mechanisms of adjuvants. 8Īlthough adjuvants have long been widely used in vaccines, the mechanisms by which they enhance immune responses have not been well characterized. 7 They have shown to enhance the strength, breadth, and persistence of immune responses in preclinical and clinical studies. 6 In addition, many other different classes of compounds had been evaluated as adjuvants during this time, including mineral salts, microbial products, emulsions, saponins, synthetic small molecule agonists, polymers, nanoparticles, and liposomes. In the following 20 years, four other adjuvants (AS04, AS03, AS01, and CpG ODN 1018) were licensed for use in vaccines, which changed the monotony of adjuvants for human vaccines. It was not until 1997 that the oil-in-water emulsion MF59 was licensed in Europe as an adjuvant for influenza vaccines. In fact, from the 1920s through the 1990s, only aluminum adjuvants were licensed, despite efforts to develop new adjuvants for human vaccines. Similar to Freund’s adjuvants, the use of bacterial lipopolysaccharide (LPS) adjuvants in human vaccines has been limited due to their local and systemic side effects. 4, 5 However, Freund’s adjuvant is not licensed for use in human vaccines because of its toxicity to humans. 3 Subsequently, in the 1940s, Freund and his colleagues developed water-in-oil emulsions, which led to the creation of Freund’s adjuvants. ![]() 2 The first evidence of adjuvants appeared in 1926, when Alexander Glenny found that mixing aluminum salts with antigens and injecting them into guinea pigs induced more antibodies than administering antigens alone (Fig. 1 Adjuvants can range from synthetic small molecule compounds to complex natural extracts and particulate materials. On this basis, this review points out the development prospects of vaccine adjuvants and the problems that should be paid attention to in the future.Īdjuvants are defined as various components that enhance the immunogenicity of vaccines when administered in conjunction with vaccine antigens (Fig. Notably, we highlight the different action mechanisms and immunological properties of these adjuvant platforms, which will provide a wide range of options for the rational design of different vaccines. Furthermore, since some of the adjuvants under investigation exhibit greater immune activation potency than classical adjuvants, which could compensate for the deficiencies of classical adjuvants, a summary of the adjuvant platforms under investigation is subsequently presented. This is followed by an introduction of the mechanisms, properties, and progress of classical vaccine adjuvants. The adjuvants’ action mechanisms are systematically summarized at the beginning of this review. ![]() On the other hand, delivery systems are carrier materials that facilitate antigen presentation by prolonging the bioavailability of the loaded antigens, as well as targeting antigens to lymph nodes or APCs. Immunostimulants are danger signal molecules that lead to the maturation and activation of antigen-presenting cells (APCs) by targeting Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) to promote the production of antigen signals and co-stimulatory signals, which in turn enhance the adaptive immune responses. Adjuvants can be categorized as immunostimulants and delivery systems. ![]() With a greater understanding of the mechanisms by which the innate immune response controls the antigen-specific response, the adjuvants’ action mechanisms are beginning to be elucidated. Despite being widely used in vaccines, their action mechanisms are not yet clear. Adjuvants are indispensable components of vaccines. ![]()
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