Notes

Here we present a summary of all the work performed to date on the mechanism of action of MF59 and we present a unified theory based on the accumulated data of how it exerts its adjuvant effects
A key element of the mechanism of action appears to be the creation of a transient 'immunocompetent' local environment at the injection site, resulting in the recruitment of key immune cells, which are able to take up antigen and adjuvant and transport them to the local lymph nodes, where the immune response is induced. This recruitment appears to be triggered by the induction of a chemokine driven gradient by the impact of MF59 on local cells, which are activated to secrete further chemokines, which are recruitment factors for more immune cells.On the mechanism of lanosterol biosynthesis from squalene 2,3-oxide.van Tamelen EE, Willett JD, Clayton RB.A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant.The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine containing recombinant PreS2 and S antigens combined with MF59 adjuvant (HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to receive 2 or 3 immunizations of either the study vaccine or a licensed control vaccine (Recombivax HB).

After a single immunization, 105 of 118 (89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs antibody (> 10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed vaccine (P < 001). The geometric mean titer (GMT) after 2 doses of HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher than that following 3 doses of licensed vaccine given over 6 months (2,346 mIU/ml; P < 001). The GMT following 3 injections of HBV/MF59 (249,917 mIU/ml) was 100-fold higher than licensed vaccine (P < 001). Anti-PreS2 antibodies were elicited in over 90% of the subset of HBV/MF59 recipients tested. Both vaccines were well tolerated; transient, mild-to-moderate local inflammation was the major postinjection Effects of arsenite on incorporation of mevalonate-2-14C into squalene-14C in Terakado M, Namiki Y, Takahashi H, Otake S, Tobe Y.834. J Biol Chem.


1961 Sep;236:2429-34.Studies on the conversion of squalene to sterol with rat liver enzymes.Regulation of ergosterol biosynthesis and sterol uptake in a sterol-auxotrophic Inhibition of sterol uptake in Saccharomyces cerevisiae sterol auxotroph FY3 (alpha hem1 erg7 ura) by delta-aminolevulinic acid (ALA) is dependent on the ability of the organism to synthesize heme from ALA. Order now -depleted cells not exposed to ALA or strain PFY3 cells, with a double heme mutation, exposed to ALA did not exhibit inhibition of sterol uptake. Addition of ALA to sterol-depleted FY3 stimulated production of a high endogenous concentration of 2,3-oxidosqualene (255 micrograms mg-1 [dry weight]) at 24 h, whereas FY3 not exposed to ALA or PFY3 exposed to ALA did not accumulate 2,3-oxidosqualene. The high concentration of 2,3-oxidosqualene in FY3 with ALA decreased, and 2,3;22,23-dioxidosqualene increased to a very high level. The elevation of 2,3-oxidosqualene by ALA was correlated with a fivefold increase in the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 14).

The enhanced activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was prevented by cycloheximide but not chloramphenicol and was dependent on a fermentative energy source. Inhibition of sterol uptake could not be attributed to 2,3-oxidosqualene or 2,3;22,23-dioxidosqualene but was due to a nonsaturating level of ergosterol produced as a consequence of heme competency through a leaky erg7 mutation.Levels of ergothioneine in the red blood cell in experimental diabetes.10016/j.ijbiomac019553. Epub 2019 May 22.Chitosan - Whey protein as efficient delivery system for squalene: Characterization and functional food application.

Squalene, a triterpenoid compound possessing excellent bioactivities, is not being utilized as a functional food ingredient due to its high susceptibility to oxidation. In l-ergothioneine mushrooms , the feasibility of chitosan-whey protein as an efficient wall material for squalene encapsulation using spray drying technique was attempted for functional food applications. The encapsulation efficiency of the squalene powder was found to be 75 ± 02% whereas other physico-chemical properties such as moisture content, flowability, solubility, peroxide value, etc. have shown satisfactory results. The thermogravimetric analysis showed that chitosan-whey protein was able to retain the thermal stability of squalene up to a temperature of 422 °C. Furthermore, the functional food application of the encapsulated squalene in a bakery product (cake) exhibited significantly (p < 05) better properties in terms of oxidative stability, sensory attributes than that of cake with pure squalene and control treatment. Hence, it can be concluded that emulsification of squalene in chitosan-whey protein and its subsequent encapsulation by spray drying can be a potential process to produce oxidatively stable encapsulates for the development of functional foods.

Noninvasive techniques for measuring oxidation products on the surface of human Precursors of squalene and cholesterol.DITURI F, RABINOWITZ JL, HULLIN RP, GURIN S.On the conversion of squalene to lanosterol in vitro.Recombinant squalene synthase.

Homepage: https://en.wikipedia.org/wiki/Ergothioneine