FLUAD® Seqirus Inc. US Package Insert
September 4, 2019 – Flu Vaccine With Adjuvant – Flu Vaccine with Adjuvant, brand name FLUAD “FLUAD is a standard-dose, three-component (trivalent) inactivated flu vaccine, manufactured by Seqirus that contains an adjuvant. FLUAD is designed specifically for people 65 years and older. It is manufactured using an egg-based process (like most flu vaccines), and is formulated with the adjuvant MF59. An adjuvant is an ingredient added to a vaccine that helps create a stronger immune response to vaccination.”
March 7, 2019 – Post-licensure surveillance of trivalent adjuvanted influenza vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United States, July 2016–June 2018 “From July 1, 2016 through June 30, 2018, VAERS received a total of 630 U.S. reports of which 521 (82.7%) were for adults aged 65 years, 79 (12.5%) were for adults aged <65 years, and 30 (4.8%) had age unspecified. aIIV3 was administered alone, without a concurrent vaccine, in 325 (62%) reports. Pneumococcal polysaccharide vaccine (PPSV) was the most commonly co-administered vaccine (n = 115; 18%) followed by pneumococcal conjugate vaccine (PCV13) (n = 69; 11%) [Table 1]. Twenty-one (3%) were serious reports, including two death reports (0.3%). Three serious reports (14%) described AEs occurring in adults aged <65 years; one of them described a case of GBS in a 32-year-old female [Table 2]. Table 3a Most frequently reported Preferred Terms following aIIV3, IIV3-HD and IIV3/IIV4 in adults aged 65 years, VAERS, July 1, 2016–June 30, 2018.a
October 26, 2017– Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus (full text) “The most common adjuvant, alum, comprised of aluminum salts, has been used in humans since 1932, is approved for human use by the FDA, and is a component of numerous licensed vaccines such as Diphtheria, Tetanus and Pertussis (DTaP) vaccines, and hepatitis B vaccines. MPLA with Alum is used for the hepatitis B vaccine, Fendrix, and the human papillomavirus (HPV)vaccine, Cervarix, and has extensive human safety data in this context. Oil-in-water formulations such as MF59 are components of FLUAD (a new seasonal flu vaccine for the elderly) MPLA is also a component of Pollinex Quattro, a vaccine used for the treatment of seasonal allergic rhinitis.”… All these groups will have been primed by natural infection, so the role of adjuvant is primarily to increase the magnitude of the response based on the established precursor T cell and B cell populations. For pregnant women, vaccination should avoid excessive Th1-biased responses for safety concerns related to the pregnancy. If adjuvants are needed to boost antibody responses to protective levels in adults, alum-based formulations may have an acceptable safety and immunological profile for use in pregnancy. In the elderly or older children, the most potent, tolerable adjuvant should be chosen based on results from early phase clinical trials.”
June 28, 2012 – More on Influenza Vaccine in Young Children “European Medicines Agency (EMA). A GCP inspection that was requested during the scientific assessment by the Committee for Medicinal Products for Human Use revealed a lack of compliance with GCP guidelines on several critical issues affecting the reliability of recorded adverse events and suspected influenza cases, as well as laboratory procedures for case confirmation, among others. Some critical data were inaccurately reported in the dossier. Novartis Vaccines and Diagnostics was unable to resolve the concerns raised within the required time and withdrew the marketing authorization application for Fluad on February 10, 2012. The report, including the assessment of deficiencies, is available both on the EMA website as part of the European Public Assessment Report and online with the full text of this letter at NEJM.org. HERE; FLUAD PAEDIATRIC Withdrawal Assessment Report (pdf) “Based on the review of the data and the Applicant response to the CHMP Day 180 LoQs on quality, safety and efficacy, the CHMP considers that the application for Fluad paediatric, for active immunization against influenza in infants and children (6 months to less than 9 years of age), is not approvable since major objections still remain, which preclude a recommendation for marketing authorisation at the present time.”
February 29, 2012 – The Vaccines and Related Biological Products Advisory Committee (VRBPAC) (pdf) “Can you comment on whether the safety profile with an MF59 adjuvanted Fluvirin-like purification molecule versus Agriflu remains the same? DR. HEATON: Fluad is Agriflu plus the adjuvant. We have certainly looked in a controlled way at the difference in the safety profile. The biggest difference is in local reactions. You do see more pain and induration with the adjuvant.
September 2011– Recommendations on the use of MF59-Adjuvanted Trivalent Influenza Vaccine (Fluad®): Supplemental Statement of Seasonal Influenza Vaccine for 2011-2012 “Mechanism of Action of Adjuvant The mechanism of action of MF59® is not fully understood. It is suggested that MF59® facilitates the internalization of antigen by dendritic cells. Footnote 2 Animal studies show that administration of MF59® triggers a cascade of immune-stimulatory events and induces a significant influx of phagocytes (e.g., macrophages and monocytes) to the site of injection, which in turn upregulates the differentiation of monocytes to dendritic cells. Footnote 8 Thus, one of the effects of MF59® is to produce a local immune-stimulatory environment at the injection site by promoting the production of immune mediators in the muscle fibers. Footnote 1, Footnote 2 This is hypothesized to be the mechanism by which the adjuvant improves and broadens the immune response.”
October 22, 2010 – Novartis Phase III study indicates MF59® adjuvanted influenza vaccine, Fluad®, is 75 percent more efficacious than studied non-adjuvanted vaccines in young children (pdf) “The most common local adverse reactions to Fluad include injection site pain, redness, swelling, ecchymosis and induration. The most common systemic reactions include fever, malaise, shivering, fatigue, headache, sweating, myalgia and arthralgia. Vaccination with Fluad may not protect all individuals. Patients with endogenous or iatrogenic immunosuppression or are undergoing immunosuppressant treatment may have an inadequate response to vaccination.”
October 16, 2008 – MF59-adjuvanted vaccines for seasonal and pandemic influenza prophylaxis (pdf)
Table 1. Incidence of reported adverse events following influenza immunization from September 1997 to August 2006
| Adverse Events | Reported cases (n) | Number of cases assessed as possibly related | Reporting rate per 100,000 does |
| All reported events | 387 | 249 | 1.4 |
| Serious cases | 107 | 34 | 0.39 |
| Fatal cases | 13 | 0 | 0.05 |
| Vaccine failures | 4 | 4 | 0.01 |
| Allergic reactions | 39 | 34 | 0.14 |
| Neurological disorders | 51 | 21 | 0.18 |
| ADEM, encephalitis, myelitis | 8 | 2 | 0.02 |
| GBS | 9 | 7 | 0.01 |
| Parsonage- Turner syndrome | 3 | 2 | 0.01 |
| Blood and vascular disorders | 9 | 2 | 0.03 |
Reproduced with permission from Schultze et al. ADEM, acute disseminated encephalomyelitis; GBS, Guillain–Barre´ syndrome.
*Sold doses of Fluad or Fluad-like vaccine 27 374 412.
June 19, 2008 – Safety of MF59™ adjuvant “A total of 750 serious adverse events were observed in the Fluad® group (i.e., 8.2%) versus 386 in the control (Influvac®) group (i.e., 8.5%).”…”Encephalitis and myelitis. Acute disseminated encephalomyelitis can follow viral and some bacterial infections and have been reported in the literature following the administration of vaccines. A total of 8 cases reported after the administration of Fluad® were under review by pharmacovigilance. There have been 2 reports of acute disseminated encephalitis, 4 additional reports of unspecified inflammatory conditions of the brain, one case ofmyelitis and one case of transversemyelitis. Two caseswere assessed as related to the vaccine.” (pgs. 8 & 11)