History of squalene use in influenza vaccines since 2009?
Executive summary
Squalene-based oil-in-water adjuvants — chiefly MF59 and AS03 — have been a part of influenza vaccine practice before and throughout the 2009 H1N1 pandemic and have continued in use since then in seasonal and pandemic formulations; regulators and multiple clinical reviews have reported acceptable safety and improved immunogenicity for certain groups [1] [2] [3]. Controversy rooted in early suspicions tying squalene to Gulf War illness diminished after larger studies and reviews found no causal link and showed that anti-squalene antibodies are commonly present in healthy people and are not significantly increased by vaccination [4] [3] [5].
1. Origins and pre-2009 footing: MF59 was already established in Europe
Squalene-containing MF59 had been used in European seasonal influenza vaccines since 1997 and by the late 2000s had been administered in the tens of millions of doses with no major safety signal reported, laying the groundwork for broader adoption during the 2009 pandemic [2] [1].
2. The 2009 pandemic: AS03 and MF59 featured in many pandemic doses
During the 2009 A(H1N1) pandemic roughly one third of pandemic vaccine formulations used adjuvants, including two squalene-based oil-in-water systems — AS03 (newer at the time) and the longer-established MF59 — to stretch antigen supplies and boost immune responses; regulators and workshop summaries noted these adjuvants’ clinically acceptable safety profiles during that emergency rollout [1].
3. Evidence on safety and immunogenicity since 2009: clinical trials and meta-analyses
A 2009 meta-analysis pooling 64 clinical trials compared MF59‑adjuvanted influenza vaccines with non‑adjuvanted equivalents and helped crystallize evidence that adjuvants increased immune responses without raising autoimmune disease rates; separate clinical trials in younger and older adults likewise reported good tolerability with typical mild local reactions [2] [3].
4. The Gulf War controversy and the antibody question: science pushed back on the alarm
Claims from earlier reports that squalene drove “Gulf War syndrome” by inducing anti‑squalene antibodies prompted targeted investigations; subsequent work, including a validated 2009 Department of Defense study and broader literature reviews, found anti‑squalene antibodies are frequently present in healthy people and saw no association between vaccination and disease, weakening the causal narrative [3] [4].
5. Continued product deployment and routine use after 2009
Adjuvanted influenza products continued to be marketed after the pandemic — for example, MF59‑adjuvanted vaccines have been positioned for older adults and were noted in product listings and public vaccine guidance in the years following 2009 — reflecting regulatory acceptance of their risk‑benefit profile for targeted populations [6] [7].
6. Public perception, misinformation, and gaps in reporting
Despite consistent clinical and regulatory reassurances, public webpages and web analyses have documented substantial misinformation and hesitancy about squalene‑based adjuvants; reviews of online content show these fears persist and influence perception even though scientific summaries emphasize low immunogenicity of squalene and lack of safety concerns [5] [2].
7. What the sources do and do not establish — limitations and open questions
Available sources document broad use of squalene adjuvants through 2009 and thereafter, clinical trial meta‑analyses supporting safety and effectiveness in specific groups, and studies rebutting earlier Gulf War linkage, but the provided material does not present exhaustive post‑2009 pharmacovigilance datasets or all country‑level adoption figures, so a complete global quantitative tally since 2009 cannot be asserted from these sources alone [2] [1] [3].