What is squalene and its role as a vaccine adjuvant?

1. Why this oily molecule matters: chemical identity and natural role that explain its use

Squalene is a linear triterpene and biochemical precursor in sterol and steroid synthesis, naturally synthesized in human tissues and concentrated in animal sources like shark liver and some plant oils; it is chemically hydrophobic and highly biocompatible, which makes it suitable as the oil phase in vaccine emulsions ^{[1] [3]}. Because squalene integrates readily into oil‑in‑water nanoemulsions it functions primarily as a physical matrix rather than a classical immune stimulant: the emulsion droplets improve antigen presentation by promoting uptake into antigen‑presenting cells and by creating a local innate immune milieu, a mechanism supported by formulation and immunology studies ^{[4] [5]}. This combination of chemical properties and biological tolerability underpins its selection over other oils for parenteral adjuvant systems.

2. The science of boost: how squalene emulsions enhance vaccine responses

Preclinical and clinical research shows squalene‑containing emulsions amplify vaccine efficacy by creating stable nano-droplets that increase antigen delivery to dendritic cells and stimulate innate signals; some studies demonstrate reactive oxygen species (ROS) generation and consequent apoptotic/necrotic cell changes that enhance antigen uptake and presentation, thereby strengthening both antibody and T‑cell responses ^{[5] [4]}. Emulsions such as MF59 and AS03 are engineered to harness these effects without squalene itself acting as a potent antigen; rather, the oil phase facilitates the adjuvant activity of the formulation, making possible antigen‑dose sparing and improved immunogenicity for influenza and other vaccines ^{[4] [3]}. The mechanistic evidence from formulation science and immunology aligns with the observed clinical benefit of these adjuvants.

3. Where it’s used and what regulators have found about safety

Squalene‑based adjuvants have been included in licensed influenza vaccines (for example, MF59‑adjuvanted Fluad) and administered in tens of millions of doses since the late 1990s, with regulatory assessments and epidemiological studies finding no causal link between squalene in vaccines and chronic multisystem illnesses; anti‑squalene antibody concerns were investigated and largely attributed to contamination artifacts rather than vaccine exposure ^{[2] [6]}. The United States has not approved squalene‑containing vaccines historically, whereas European regulators and manufacturers have relied on squalene emulsions to extend vaccine supply and augment immune responses, and long‑term safety literature and reviews support a favorable safety profile when used in licensed formulations ^{[2] [3]}.

4. Controversy, myths, and settled science around Gulf War claims

Squalene became controversial after claims that it caused Gulf War Illness; subsequent investigations found no credible evidence that vaccine-delivered squalene triggered the syndrome, and laboratory contamination explained early reports of anti‑squalene antibodies in affected veterans. Peer‑reviewed surveillance and clinical studies failed to show increased anti‑squalene immunity attributable to vaccines, and public‑health reviews concluded the association was unsupported by the data ^{[6] [2]}. The controversy highlights how trace‑level laboratory artifacts and non‑reproducible findings can fuel public concern, but systematic evaluations and regulatory oversights have not substantiated harms from licensed squalene‑emulsion vaccines.

5. Sourcing, environmental stakes, and the move to alternatives

Squalene traditionally came from shark liver oil, raising conservation and ethical concerns about shark populations and ecosystem impacts; that pressure, combined with commercial and regulatory preference for sustainable sourcing, has driven development of plant‑derived and synthetic squalene sources and increased interest in alternative adjuvant chemistries ^{[7] [1]}. The literature and industry reports document a shift toward plant-based squalene and improved supply chains to reduce reliance on sharks, while scientific work continues to refine formulations that maximize immunological benefit and minimize ecological cost ^{[7] [4]}. These supply‑chain realities shape both public perception and practical deployment of squalene‑adjuvanted vaccines during high-demand periods.

Summary comparison of claims and evidence: authoritative biochemistry and immunology sources characterize squalene as a natural, chemically suited oil used in emulsion adjuvants that enhance antigen uptake and immune responses; regulatory and epidemiologic records document a long safety record and debunked earlier claims linking it to Gulf War illness, and contemporary debate centers on sustainable sourcing rather than intrinsic toxicity ^{[1] [4] [5] [2] [7] [3]}.