Squalene and squalane emulsions as adjuvants.
Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.
Allison
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AC
SurroMed Corporation, 1060 East Meadow Circle, Palo Alto, California 94303, USA. anthony@surromed.com
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage; D004655:Emulsions; D006801:Humans; D007111:Immunity, Cellular; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D009369:Neoplasms / Q000628:therapy; D011108:Polymers / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage* / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000941:Antigens; D019496:Cancer Vaccines; D004655:Emulsions; D007132:Immunoglobulin Isotypes; D011108:Polymers; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D013185:Squalene