Abstract
The concept of adjuvants or adjuvant systems, used in vaccines, exploit evolutionary relationships associated with how the immune system may initially respond to a foreign antigen or pathogen, thus mimicking natural exposure. This is particularly relevant during the non-specific innate stage of the immune response; as such, the quality of this response may dictate specific adaptive responses and conferred memory/protection to that specific antigen or pathogen. Therefore, adjuvants may optimise this response in the most appropriate way for a specific disease. The most commonly used traditional adjuvants are aluminium salts; however, a biodegradable adjuvant, MCT®, was developed for application in the niche area of allergy immunotherapy (AIT), also in combination with a TLR-4 adjuvant—Monophosphoryl Lipid A (MPL®)—producing the first adjuvant system approach for AIT in the clinic. In the last decade, the use and effectiveness of MCT® across a variety of disease models in the preclinical setting highlight it as a promising platform for adjuvant systems, to help overcome the challenges of modern vaccines. A consequence of bringing together, for the first time, a unified view of MCT® mode-of-action from multiple experiments and adjuvant systems will help facilitate future rational design of vaccines while shaping their success.
Highlights
The Evolution of Vaccines and AdjuvantsThe concept of variolation dates back to the 10th century in China, here, immunization against small pox used the live virus itself
Pattern recognition receptors (PRRs) on innate and adaptive immune cells [i.e., macrophages, dendritic cells (DCs), monocytes, neutrophils, and B cells] have evolved to recognise conserved features that are typical of pathogenic surface patterns [pathogen-associated molecular patterns (PAMPs)], being able to signal an incoming agent as a threat, that is distinguishable from “self” [16, 36, 37]
The most effective way to treat IgE-mediated allergies is through allergenspecific immunotherapy (AIT), which entails repeated administration of specific allergens to patients resulting in protection against the allergic and inflammatory reactions [41]
Summary
The concept of variolation (human inoculation/insertion of pathogens) dates back to the 10th century in China, here, immunization against small pox used the live virus itself. As part of Glenny’s work dealing with bacterial toxins, metal salts (precipitates thereof) were employed during the purification process, the adsorbed toxoid was subject to the wisdom of Glenny to perform comparative immunological studies, which indicated greatly enhanced immunological effects [14, 17], illuminating the serendipitous points of discovery that have shaped the modern world. Tools to study the genome or cellular systems have developed rapidly This has inspired new strategies from empirical to rational approaches to vaccine design and antigen carrier (nano)-systems, for targeting both innate and adaptive immune responses in tackling more challenging or emerging diseases or improvements in safety and efficacy of others [27,28,29]. The development of new and sophisticated rational technologies such as antigen (nano)-carrier systems [e.g., virus-like particles (VLPs)] or combination of adjuvants (adjuvant systems) are being employed to help overcome these challenges [29, 35]
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