Unraveling the enigma: elucidating the relationship between the physicochemical properties of aluminium-based adjuvants and their immunological mechanisms of action

Abstract

Aluminium salts are by far the most commonly used adjuvants in vaccines. There are only two aluminium salts which are used in clinically-approved vaccines, Alhydrogel® and AdjuPhos®, while the novel aluminium adjuvant used in Gardasil® is a sulphated version of the latter. We have investigated the physicochemical properties of these two aluminium adjuvants and specifically in milieus approximating to both vaccine vehicles and the composition of injection sites. Additionally we have used a monocytic cell line to establish the relationship between their physicochemical properties and their internalisation and cytotoxicity. We emphasise that aluminium adjuvants used in clinically approved vaccines are chemically and biologically dissimilar with concomitantly potentially distinct roles in vaccine-related adverse events.

The size of micro-crystalline tyrosine (MCT®) influences its recognition and uptake by THP-1 macrophagesin vitro

“…linked to the suppression of IL-18 secretion. 47 While further studies are required in order to fully validate these suppositions, these SARs may provide an initial explanation regarding the ability of MCT® to promote the class-switch recombination mechanisms required to ameliorate allergic responses whilst minimising local side-effects following administration. One documented advantage of MCT® in SCIT as oppose to traditional aluminium salts is its rapid relative elimination from the site of injection via the bloodstream, typically within one week of administration.…”

“…35 How particulate adjuvants facilitate the polarisation and potentiation of the immune response during vaccination is yet to be fully elucidated; however, postulated mechanisms include the induction of pro-inammatory cytokine secretion through activation of the NALP-3 inammasome, [36][37][38][39] depot formation 35,40,41 and improved antigenic cross-presentation through enhanced recognition and uptake by antigen presenting cells (APCs). [42][43][44][45][46] Recent literature has highlighted the importance of particulate physicochemistry with regards to the subsequent biological activity of adjuvants administered as colloidal suspensions (see review 47 ). Properties which signicantly inuence the adjuvanticity of such materials include solid-state structure, particle size, particle shape and zeta potential.…”

“…Properties which signicantly inuence the adjuvanticity of such materials include solid-state structure, particle size, particle shape and zeta potential. 14,47 The hydrodynamic particle size of adjuvants is particularly important with regards to the recognition of such material by immunocompetent cells at the site of injection, a precursor to particulate uptake and cellular translocation to the draining lymph nodes. 47 In order to increase the understanding of the mechanisms by which MCT® promotes desensitisation in SCIT, this is the rst study to fully characterise the physicochemical properties of MCT® and examine their inuence, especially that of particle size, upon the cellular recognition of this adjuvant in vitro.…”

Aluminum Nanoparticles Acting as a Pulmonary Vaccine Adjuvant-Delivery System (VADS) Able to Safely Elicit Robust Systemic and Mucosal Immunity

“…The gel-like alum adjuvants may not fit certain administration modes, such as pulmonary vaccination, since their sticky property is likely to cause bronchoalveolar airway obstruction. Moreover, alums have another two disadvantages: they are a strong antibody adjuvant but unable to induce cellular reactions; they sometimes stimulate unacceptable local irritations as side effects [33]. As a result of this, researchers are now making efforts on reformulation of conventional alums to improve their adjuvanticity.…”

The use of aluminium hydroxide as adjuvant modulates the specific antibody response—A Brown Norway rat study with native and denatured cow's milk allergens

“…Traditionally, adjuvant is a common constituent of IT vaccines, where aluminium hydroxide (Al(OH) 3 ) is standard use 24‐26 . Although the mechanisms underlying the adjuvanticity of Al(OH) 3 is far from being fully understood, adsorbance of allergens to Al(OH) 3 is widely used due to the repository effect and to the increase in immune response towards the co‐formulated allergen.…”