Some notable adjuvants
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MF59TM is a sub-micron oil-in-water emulsion of a squalene, polyoxyethylene sorbitan monooleate (TweenTM 80) and sorbitan trioleate. Squalene is a natural organic compound originally obtained from shark liver oil and a biochemical precursor to steroids. The MF59 adjuvant was developed by Chiron Corp., a company acquired by Novartis. MF59 is approved in Europe and is found in several vaccines, such as an influenza vaccine manufactured by Novartis. It has also been licensed to other companies and is being actively tested in vaccine trials.
Other oil-in-water emulsions include Montanide (Seppic), Adjuvant 65 (in use since the 1960s), and Lipovant.
AS02 and AS04 are proprietary adjuvants of GlaxoSmithKline (GSK). AS02 contains MPLTM and QS-21 in an oil-in-water emulsion. AS02 is used in a malaria vaccine of GSK. AS04 also is composed of MPL, but in combination with alum. This adjuvant is used in GSK's HSV and HPV vaccine. MPL was developed by Corixa Corp., a company purchased by GSK in order to secure MPL production for GSK vaccines. MPL is composed of a series of 4'-monophosphoryl lipid A species that vary in the extent and position of fatty acid substitution. It is prepared from lipopolysaccharide (LPS) of Salmonella minnesota R595 by treating LPS with mild acid and base hydrolysis followed by purification of the modified LPS.
QS-21- A natural product of the bark of the Quillaja saponaria tree species, which is native to Chile and Argentina. QS-21 is being tested in clinical trials with a wide variety of vaccine antigens. Originally patented by Cambridge Biotech Corp., which went into bankruptcy and spun out its therapeutic immune system business into Aquila Biopharmaceuticals, the patents were acquired by Antigenics, Inc. in a buy-out of Aquila. According to Antigenics, QS-21 is licensed by corporate partners, including GlaxoSmithKline, Wyeth, and Aventis Pasteur. In return for rights to use the QS-21 adjuvant for specific diseases, the corporate partnershave agreed to pay Antigenics license fees, milestone payments, and royalties on product sales.
ISCOMs is an acronym meaning immune stimulating complexes. ISCOMs are honeycomb-like structures composed of typically Quillaja saponins, cholesterol, phospholipid and antigen. Some ISCOMs are pre-formed without antigen and then mixed with antigen such that the antigen is absorbed onto or conjugated to the ISCOM. ISCOMs were initially developed in the mid-1980s by Iscotec, a company in Sweden.
Unmethylated CpG dinucleotides are the reason that bacterial DNA, but not vertebrate DNA, is immunostimulatory. Vertebrate DNA has relatively low amounts of unmethylated CpG compared to bacterial DNA. The adjuvant effect of CpG is enhanced when conjugated to protein antigens. CPG7909, an adjuvant developed by Coley Pharmaceuticals has been tested in a few vaccines, an alum-adjuvanted Hepatitis B vaccine and a CpG adjuvanted melanoma vaccine.
ADVAX, an adjuvant developed at Vaxine Pty Ltd. in Australia, is based on inulin, a natural plant-derived polysaccharide consisting of a chain of fructose molecules ending in a single glucose. Specific isoforms, gamma- and delta-inulin, are prepare and formulated into compositions suitable as adjuvants. For example, one formuation of gamma inulin is a pure suspension of sub-micron particles. A synergistic effect is obtained by combining gamma-inulin with an antigen-binding material, such as inulin. This adjuvant is called Algammulin. Vaxine has several patent families directed to both the gamma and delta forms of inulin and is using them in vaccine trials.
The information contained in this page was believed to be correct at the time it was collated. New patents and patent applications, altered status of patents, and case law may have resulted in changes in the landscape. CAMBIA makes no warranty that it is correct or up to date at this time and accepts no liability for any use that might be made of it. Corrections or updates to the information are welcome. Please send an email to info@bios.net.
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