1/3/2024 0 Comments Al oh 3 precipitate![]() ![]() Here, we confirm that Al(OH) 3 activates the complement system and show that aluminum hydroxide adjuvant activates the three complement pathways with major involvement of the alternative complement pathway, thus providing a rationale for its efficient adjuvant properties.Īl(OH) 3 (Alhydrogel®, sterile and free of pyrogens) was from Brenntag Biosector (Frederikssund, Denmark). * Initial alternative C3 convertase generated from C3(H 2O) and fB. The C3 convertase cleaves C3 generating C3b and enables assembly of a C5 convertase (C3bC3bBb or C4bC2aC3b), and the C5-convertase product (C5b) initiates assembly of the membrane attack complex (MAC) from C5b-C9. The CP is initiated by C1q recognition of immune complexes, activating C1r and C1s, again cleaving C4 and C2 generating a C3 convertase characteristic of the CP and the LP (C4bC2a). The first component of the classical pathway (CP) is C1, a complex of C1q and its associated serine proteases C1r and C1s. The lectin pathway (LP) is activated when MBL or other immune lectins bind carbohydrates on pathogens, activating the associated serine proteases (MASPs) which cleave C4 and C2. The C3 convertase generates C3b and the subsequent C3-convertases are assembled by C3b and Bb. The alternative C3-convertase is stabilized by properdin (P). The alternative pathway (AP) is activated when C3 undergoes spontaneous hydrolysis and forms the initial C3 convertase, C3(H 2O)Bb in the presence of factor B (fB) and cleavage of bound fB by factor D (fD). The three pathways of complement activation. On the contrary, Tengvall et al., found no evidence that complement deposition on aluminium hydroxide occurred as a result of complement activation (the three major complement pathways are described in Fig. However, findings by Arvidsson et al., suggested that an aluminum surface binds C3 through the classical complement pathway. This was later confirmed by Ramanathan et al., who found that aluminum and zirconium compounds could activate the complement system and it was suggested that the complement activation occurred through the lectin pathway. Already in 1975, Polley and Nachman observed that aluminum hydroxide could remove 40–60% of the haemolytic complement activity in a serum sample. Aluminum hydroxide has also been described to be able to activate the complement system. Recently, aluminum hydroxide has been observed to bind lipid moieties on dendritic cells and promote lipid sorting in the plasma membrane, leading to signal transduction and immune response initiation and increase antigen uptake and enhance antigen presentation on dendritic cells, and directly affect B lymphocytes. Other non-exclusive modes of action have also been suggested, including enhancement of antigen uptake and presentation, innate immune system activation and enhancement of cytokine production and release –, –. initially described the adjuvant effect of aluminium adjuvants to be due to the ability of these to form a depot and to control the release of antigen this has later been questioned. ![]() The modes of action of aluminum adjuvants are still a subject of research but several mechanisms have been suggested. Among the few approved adjuvants for human vaccines the aluminum compounds are often preferred and have been used extensively for diphtheria vaccines, tetanus vaccines, pertussis vaccines, hepatitis vaccines and polio vaccines –. and the effect has been used in vaccines since the first half of the 20 th century (from around 1930). The first adjuvant effect of an aluminum compound was described by Glenny et al. They include CpG DNA, ssDNA, dsRNA and bacterial cell wall components. Also, the pathogen-associated molecular patterns (PAMPs) are a big group of naturally occurring compounds with adjuvant properties. aluminium hydroxide (Al(OH) 3), the hydrated form of aluminium oxide (Al 2O 3) –. Many different compounds of both organic and inorganic origin have been observed to stimulate a vigorous immune response and therefore have adjuvant properties these include mineral oils and different metal salts, notably aluminum compounds (e.g. Immunological adjuvants are compounds which initiate and boost immune responses, leading to stronger and faster adaptive immune responses without having any antigenic effect by themselves. ![]()
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