Enhancement of humoral response against human influenza vaccine with the simple submicron oil/water emulsion adjuvant MF59.
Human influenza subunit vaccines are not fully protective in either the very young or elderly populations where risk is greatest. The use of an adjuvant to enhance antibody titer is an attractive option to increase vaccine efficacy. A series of squalene/H2O emulsions stabilized either by the amphipathic muramyl peptide MTP-PE (sodium N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanyl-2-(1',2'-dipalmitoyl- sn- glycero-3'phospho) ethylamide) or by mixtures of the sorbitan oleate surfactants Tween 80 and Span 85 have been tested as adjuvants with influenza vaccine. Combination of influenza vaccine with the Tween/Span stabilized emulsions has resulted in significantly higher antibody titers to vaccine in an extensive series of naive animal models. The use of submicron emulsion droplets is significant in determination of adjuvant activity while the presence of the muramyl peptide is not required for adjuvant activity. The 200-300 nm diameter emulsion formulation MF59 containing only the low toxicity components squalene, Tween 80 and Span 85 has been shown to enhance titers from 5 to 250 times that achievable with vaccine alone.
Ott
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Chiron Corporation, Emeryville, CA 94608, USA.
Barchfeld
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Van Nest
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D013185:Squalene / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004655:Emulsions; D007252:Influenza Vaccines; D010714:Phosphatidylethanolamines; D014867:Water; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D013185:Squalene