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AS03
AS03 (for "Adjuvant System 03") is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline (GSK). It is used, for example, in GSK's A/H1N1 pandemic flu vaccine Pandemrix. It is also in Arepanrix and the Q-pan for H5N1 influenza. A dose of AS03 adjuvant containsPandemrix – Summary of product characteristics
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European Medicines Agency website
* 10.69 mg
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Immunologic Adjuvant
In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word ''adiuvare'', meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens." In the early days of vaccine manufacture, significant variations in the efficacy of different batches of the same vaccine were correctly assumed to be caused by contamination of the reaction vessels. However, it was soon found that more scrupulous cleaning actually seemed to ''reduce'' the effectiveness of the vaccines, and some contaminants actually enhanced the immune response. There are many known adjuvants in widespread use, including aluminium salts, oils and virosomes. Overview Adjuvants in immunology are often used to modify or augment the effects of a vaccine by stimulating the immune system to re ...
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Squalene
Squalene is an organic compound. It is a triterpenoid with the formula C30H50. It is a colourless oil, although impure samples appear yellow. It was originally obtained from shark liver oil (hence its name, as ''Squalus'' is a genus of sharks). All plants and animals produce squalene as a biochemical intermediate to sterol biosynthesis. An estimated 12% of bodily squalene in humans is found in sebum. Squalene has a role in topical skin lubrication and protection. Squalene is a precursor for synthesis of all plant and animal sterols, including cholesterol and steroid hormones in the human body. Squalene is an important ingredient in some vaccine adjuvants: The Novartis and GlaxoSmithKline adjuvants are called MF59 and AS03, respectively. Role in steroid synthesis Squalene is the biochemical precursor to steroids. The squalene conversion begins with oxidation (via squalene monooxygenase) of one of its terminal double bonds, resulting in 2,3-oxidosqualene. It then undergoes an ...
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Pandemrix
Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006. The vaccine was one of the H1N1 vaccines approved for use by the European Commission in September 2009, upon the recommendations of the European Medicines Agency (EMEA). The vaccine is only approved for use when an H1N1 influenza pandemic has been officially declared by the World Health Organization (WHO) or European Union (EU). The vaccine was initially developed as a pandemic mock-up vaccine using an H5N1 strain. Pandemrix was found to be associated with an increased risk of narcolepsy following investigations by Swedish and Finnish health authorities and had higher rates of adverse events than other vaccines for H1N1. This resulted in several legal cases. Stanford University studies suggested that narcolepsy is an autoimmune disease and that it appears to be triggered by upper airway respiratory infection ...
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Pandemic Flu
An influenza pandemic is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The most recent, the 2009 swine flu pandemic, resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly. Influenza pandemics occur when a new strain of the influenza virus is transmitted to humans from another animal species. Species that are thought to be important in the emergence of new human strains are pigs, chickens and ducks. These novel strains are unaffected by any immunity people may have to older strains of human influenza and can therefore spread extremely rapidly and infect very large numbers of people. Influenza A viruses can occasio ...
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MF59
MF59 is an immunologic adjuvant that uses squalene. It is Novartis' proprietary adjuvant that is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells. MF59 is the first oil-in-water influenza vaccine adjuvant to be commercialized in combination with a seasonal influenza virus vaccine. MF59 is used as an adjuvant in Canada, Europe and the United States. MF59 was developed in the 1990s by researchers at Chiron Corporation, a Novartis heritage company, acquired by Novartis in 2006.MF59 Adjuvant Fact Sheet


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AS04
Adjuvant System 04 or AS04 is a trade name for combination of adjuvants used in various vaccine products by GlaxoSmithKline, in particular the Fendrix hepatitis B vaccine. It is also one of the ingredients of the human papillomavirus vaccine (HPV). Studies of AS04-adjuvanted HPV vaccine showed high and justified immune response against to HPV antigens. Furthermore, patients who took HPV-16/18 AS04-adjuvanted vaccine previously showed strong rapid responses upon receiving subsequent doses. It consists of aluminum hydroxide and monophosphoryl lipid A (MPL). Furthermore, it is the successor of AS03 which is a squalene based adjuvant approved for pandemic vaccine by the EMA. The heightened immune response was caused by the MPL component in AS04 which increased NF-kB and cytokine production. The aluminum hydroxide component in AS04 made the response last for a longer period of time. This is the reason why the HPV-16/18 AS04-adjuvanted vaccine was shown to be more efficient compared ...
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GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tenth largest pharmaceutical company and #294 on the 2022 ''Fortune'' Global 500, ranked behind other pharmaceutical companies China Resources, Sinopharm, Johnson & Johnson, Pfizer, Roche, AbbVie, Novartis, Bayer, and Merck. The company has a primary listing on the London Stock Exchange and is a constituent of the FTSE 100 Index. , it had a market capitalisation of £70 billion, the eighth largest on the London Stock Exchange. It has a secondary listing on the New York Stock Exchange. The company developed the first malaria vaccine, RTS,S, which it said in 2014 it would make available for five percent above cost. Legacy products developed at GSK include several listed in the World Health Organization's List of Essential Medicines, such ...
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A/H1N1
In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the Spanish flu, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxovirus that contains the glycoproteins hemagglutinin and neuraminidase. For this reason, they are described as H1N1, H1N2 etc., depending on the type of H or N antigens they express with metabolic synergy. Hemagglutinin causes red blood cells to clump together and binds the virus to the infected cell. Neuraminidase is a type of glycoside hydrolase enzyme which helps to move the virus particles through the infected cell and assist in budding from the host cells. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza, for instance in 2004–2005. Other strains of H1N1 are endemic in pigs (swine influenza) and in birds (avian influenza). Its size is in d ...
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European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or European Medicines Evaluation Agency (EMEA).Set up by EC Regulation No. 2309/93 as the European Agency for the Evaluation of Medicinal Products, and renamed by EC Regulation No. 726/2004 to the European Medicines Agency, it had the acronym EMEA until December 2009. The European Medicines Agency does not call itself EMA either – it has no official acronym but may reconsider if EMA becomes commonly accepted (secommunication on new visual identity an). The EMA was set up in 1995, with funding from the European Union and the pharmaceutical industry, as well as indirect subsidy from member states, its stated intention to harmonise (but not replace) the work of existing national medicine regulatory bodies. The hope was that this plan would not o ...
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α-tocopherol
α-Tocopherol is a type of vitamin E. It has E number "E307". Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes. Compared to the others, α-tocopherol is preferentially absorbed and accumulated in humans. Vitamin E is found in a variety of tissues, being lipid-soluble, and taken up by the body in a wide variety of ways. The most prevalent form, α-tocopherol, is involved in molecular, cellular, biochemical processes closely related to overall lipoprotein and lipid homeostasis. Ongoing research is believed to be "critical for manipulation of vitamin E homeostasis in a variety of oxidative stress-related disease conditions in humans." One of these disease conditions is the α-tocopherol role in the use by malaria parasites to protect themselves from the highly o ...
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Polysorbate 80
Polysorbate 80 is a nonionic surfactant and emulsifier often used in pharmaceuticals, foods, and cosmetics. This synthetic compound is a viscous, water-soluble yellow liquid. Chemistry Polysorbate 80 is derived from polyethoxylated sorbitan and oleic acid. The hydrophilic groups in this compound are polyethers also known as polyoxyethylene groups, which are polymers of ethylene oxide. In the nomenclature of polysorbates, the numeric designation following polysorbate refers to the lipophilic group, in this case, the oleic acid (see polysorbate for more detail). The full chemical names for polysorbate 80 are: *Polyoxyethylene (20) sorbitan monooleate *(x)-sorbitan mono-9-octadecenoate poly(oxy-1,2-ethanediyl) The critical micelle concentration of polysorbate 80 in pure water is reported as 0.012 mM. Other names E number: E433 Brand names: *Kolliphor PS 80 - Kolliphor is a registered trademark of BASF *Alkest TW 80 *Scattics *Canarcel *Poegasorb 80 *Montanox 80 – Montano ...
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2009 Influenza Pandemic
The 2009 swine flu pandemic, caused by the H1N1 influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, is the third recent flu pandemic involving the H1N1 virus (the first being the 1918–1920 Spanish flu pandemic and the second being the 1977 Russian flu). The first two cases were discovered independently in the United States in April 2009. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term "swine flu". Some studies estimated that the real number of cases including asymptomatic and mild cases could be 700 million to 1.4 billion people—or 11 to 21 percent of the global population of 6.8 billion at the time. The lower value of 700 million is more than the 500 million people estimated to have been infected by the Spanish flu pandemic. However, the Spanish flu infected approximat ...
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