Squalene is a naturally occurring oil which has been used in the development of vaccine adjuvants, such as the oil-in-water emulsion MF59. In past years, by use of noncontrolled and nonvalidated assays, a claim was made that antisqualene antibodies were detectable in the sera of individuals with the so-called Gulf War syndrome. Using a validated enzyme-linked immunosorbent assay for the quantitation of immunoglobulin G (IgG) and IgM antibodies against squalene, we demonstrated that antisqualene antibodies are frequently detectable at very low titers in the sera of subjects who were never immunized with vaccines containing squalene. More importantly, vaccination with a subunit influenza vaccine with the MF59 adjuvant neither induced antisqualene antibodies nor enhanced preexisting antisqualene antibody titers. In conclusion, antisqualene antibodies are not increased by immunization with vaccines with the MF59 adjuvant. These data extend the safety profile of the MF59 emulsion adjuvant.Squalene is a triterpenoid hydrocarbon oil (C 30 H 50 ) produced by plants and is present in many foods. Squalene is also produced abundantly by human beings, for whom it serves as a precursor of cholesterol and steroid hormones (8) It is synthesized in the liver and the skin, transported in the blood by very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL), and secreted in large amounts by sebaceous glands (10,17).Since it is a natural component of the human body and is biodegradable, squalene has been used as a component of vaccine adjuvants. One of these adjuvants is MF59, an oil-inwater emulsion developed by Chiron (14). MF59 has been shown in various preclinical and clinical studies to significantly enhance the immune response to a wide variety of vaccine antigens (15). MF59 is a part of an influenza subunit vaccine which has been licensed in various European countries since 1997. More than 20 million doses of this vaccine have been given, and it has been shown to have an excellent safety profile. The safety of vaccines with the MF59 adjuvant has also been shown by various investigational clinical studies using recombinant antigens from hepatitis B virus, hepatitis C virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, uropathogenic Escherichia coli, etc., with various age groups, including 1-to 3-day-old newborns (16).In 2000, antisqualene antibodies were reported to be present in the sera of veterans returning from the first Persian Gulf War with a series of symptoms diagnosed by the authors of the report as representing the so-called Gulf War syndrome (4). The conclusions of this work, based on Western blot assays, were severely criticized on technical grounds (1) and were considered inconclusive by the Institute of Medicine (7).Despite the fact that vaccines given to veterans returning with Gulf War syndrome did not contain squalene (6) and despite that fact that symptoms similar to those of the so-called Gulf War syndrome have been reported after several wars, including the American...
