Global Vaccine Safety

Safety of squalene

Extract from report of GACVS meeting of 6-7 June 2006, published in the WHO Weekly Epidemiological Record on 14 July 2006

Squalene is a component of some adjuvants that is added to vaccines to enhance the immune response. A naturally occurring substance found in plants, animals and humans, squalene is synthesized in the liver and circulates in the human bloodstream. It is also found in a variety of foods, cosmetics, over-the-counter medications and health supplements. Squalene is commercially extracted from fish oil – in particular shark-liver oil – and is purified from this source when used in pharmaceutical products and vaccines.

Squalene alone is not an adjuvant, but emulsions of squalene with surfactants enhance the immune response when added to antigens. MF59, a proprietary adjuvant containing squalene, is included in a seasonal subunit influenza vaccine licensed by the Italian regulatory authority in 1997 and subsequently by several other countries. The vaccine contains about 10 mg of squalene per dose. Over 22 million doses have been distributed since that time. Reported rates of adverse events and local reactogenicity are not in excess of those that would be expected with other inactivated seasonal flu vaccines, suggesting that squalene in this vaccine poses no significant risk. This vaccine has been administered primarily to individuals aged 65 years and older, for whom the vaccine was licensed.

Several experimental vaccines, including some pandemic flu vaccines, malaria vaccines, and various viral and bacterial vaccines, are also being developed with squalene-containing adjuvants, with the intention of enhancing immunogenicity and thereby efficacy. Clinical studies of squalene-containing vaccines have been performed in infants and neonates without evidence of safety concerns.

A link between the health problems of Gulf-War veterans and possible presence of squalene in vaccines received by these soldiers has been suggested. One published report has suggested that some army veterans who received anthrax vaccines developed anti-squalene antibodies and that these antibodies caused disabilities. However, squalene was not added to the vaccines administered to these veterans, nor was it used in the manufacturing process. Various papers have been published outlining the technical deficiencies in that original report.

Most adults, particularly older ones, irrespective of their history of vaccination, have naturally occurring antibodies reacting with squalene. In a clinical trial, immunization with the licensed influenza vaccine containing squalene did not affect the frequency or titre of anti-squalene antibodies.

The Committee concurred that fears of squalene in vaccine-inducing pathological anti-squalene antibodies are unfounded. It did note, however, that the experience of squalene-containing vaccines has been primarily in older age-groups and recommended that as squalene-containing vaccines are introduced in other age-groups, careful post-marketing follow up to detect any vaccine-related adverse events needs to be performed.