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MPL™ Adjuvant |
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Vaxjo ID |
24 |
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Vaccine Adjuvant Name |
MPL™ Adjuvant |
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Alternative Names |
3-Q-desacyl-4'-monophosphoryl lipid A; 3D-MLA |
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Adjuvant VO ID |
VO_0001250
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Description |
MPL adjuvant is a chemically modified derivative of lipopolysaccharide that displays greatly reduced toxicity while maintaining most of the immunostimulatory activity of lipopolysaccharide. MPL adjuvant has been used extensively in clinical trials as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies (Evans et al., 2003). MPL is a potent stimulator of T cell and antibody responses. MPL is the first and only TLR ligand in licensed human vaccines, in the form of AS04. MPL is licensed in Europe for allergy treatment Pollinex Quattro. MPL adjuvants have been given to thousands of individuals, and are safe, well-tolerated and potent (Dubensky and Reed, 2010). |
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Stage of Development |
Clinical Trial |
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Components |
Recently it has been demonstrated that monophosphoryl lipid A (MPL), a 3-deacylated monophosphoryl lipid A, derived from the lipopolysaccharide (LPS) of Salmonella minnesota, in conjugation with antigens adsorbed to L- tyrosine, induced a Th1-skewed immune response and also led to enhanced IgG responses (Mothes et al., 2003). |
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Structure |
MPLTM is composed of a series of 4'-monophosphoryl lipid A species that vary in the extent and position of fatty acid substitution. The hexaacyl structure shown below is the most highly acylated and most abundant component in MPLO. Species with five and four fatty acids are also present. All structures contribute to the adjuvant activity of MPLO (Vogel and Powell, 1995). |
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Molecular Weight |
1540-1670 (avera |
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Appearance |
Colorless, odorless white powder. |
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Storage |
Indefinite stability as Iyophilized powder (in excess of 5 years if stored at 5°C). Available data indicates stability in aqueous solution is maximum between pH 5-6. An aqueous formulation was stable (< 10% loss of most highly acylated component) for the equivalent of 2-3 years in an accelerated stability study (Vogel and Powell, 1995). |
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Preparation |
Derived from the lipopolysaccharide (LPS) of Salmonella minnesota R595. Obtained by treatment of LPS with mild acid and base hydrolytic conditions, and chromatographic purification of the resulting 3D-MLA (Vogel and Powell, 1995). |
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Dosage |
50 μg of MPL (AS04) was used in pre-clinical mice (Giannini et al., 2006). |
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Function |
Classical aluminium salts have been used for many years in vaccine formulations, but in contrast to more recently developed adjuvants, aluminium salts are not capable of activating the pro-inflammatory cytokines implicated in the innate immunity. Nevertheless, aluminium salts do induce the production of IL-4, which plays a key role in humoral responses. However, like LPS, MPL has been shown to be capable of binding and activating the so-called Toll-like receptor-4 (TLR-4), present on key antigen-presenting cells, which play an important role in the induction of the innate and subsequent adaptive immune responses. Recent observations suggest that TLR4 agonist, such as MPL, directly affect adaptive immune responses via specific interactions with B cells. Based on the current data demonstrating similar relative boost ability of total antibody responses with Alum and AS04 formulations it is very likely that VLPs complement the ability of MPL to enhance the humoral immune responses (Giannini et al., 2006). |
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Safety |
With over 33,000 doses administered to date, MPL adjuvant has emerged as a safe and effective vaccine adjuvant (Evans et al., 2003). |
| Related Vaccine(s) |
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| References |
Dubensky and Reed, 2010: Dubensky TW Jr, Reed SG. Adjuvants for cancer vaccines. Seminars in immunology. 2010; 22(3); 155-161. [PubMed: 20488726].
Evans et al., 2003: Evans JT, Cluff CW, Johnson DA, Lacy MJ, Persing DH, Baldridge JR. Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi.529. Expert review of vaccines. 2003; 2(2); 219-229. [PubMed: 12899573].
Giannini et al., 2006: Giannini SL, Hanon E, Moris P, Van Mechelen M, Morel S, Dessy F, Fourneau MA, Colau B, Suzich J, Losonksy G, Martin MT, Dubin G, Wettendorff MA. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006; 24(33-34); 5937-5949. [PubMed: 16828940].
Mothes et al., 2003: Mothes N, Heinzkill M, Drachenberg KJ, Sperr WR, Krauth MT, Majlesi Y, Semper H, Valent P, Niederberger V, Kraft D, Valenta R. Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2003; 33(9); 1198-1208. [PubMed: 12956739].
Vogel and Powell, 1995: Vogel FR, Powell MF. A compendium of vaccine adjuvants and excipients. Pharmaceutical biotechnology. 1995; 6; 141-228. [PubMed: 7551218].
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