Mf59 is an oilinwater mixture of squalene and surfactants soaplike chemicals. Compared to alum, mf59 adjuvanted influenza vaccine induced higher levels of antigenspecific antibody production, higher hai titers, and better protection in a mouse model. Yet, rational vaccine design involves a logical choice of adjuvant based on a knowledge of their mode of action and. The oil used for mf59 is squalene, naturally occurring biodegradable and biocompatible oil. Moreover, adjuvant potency was also impacted by emulsion composition, since sea160 and mf59 160 nm, also induced higher titers than mfa160 160 nm mfa160 mf59, because sea160 and. The adjuvant mf59 1 is an oilinwater emulsion stabilized by tween 80 and span 85 that converts immune cells into antigenpresenting cells and also promotes tcell activation and bcell expansion. To obtain the indicated vaccine compositions, appropriate volumes of h7n9c ha supplied as a prefilled vial of 15.
Submicron emulsions based on mf59 novartis is the first oilinwater vaccine adjuvant to be commercialized in combination with seasonal influenza virus vaccine ott et al. Squalene is an oil more readily metabolized than the paraffin oil used in freunds adjuvants 1. In contrast to existing books on the subject, the chapters here provide summaries of key data on the mechanisms of action of the. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Addavax mf59 like squalene adjuvant for vaccine research. Yeast cells have been genetically engineered to produce commercially useful quantities of. The adjuvant effect of mf59 is due to the oilinwater. Information contained herein is not to be used for commercial purposes objective provide an overview of the mf59 oilinwater emulsion adjuvant, providing insights. We randomly allocated adults aged 1840 years without hiv infection and at low risk of hiv infection to either the vaccine regimen intramuscular injection of alvachiv vector vcp2438 at 0, 1, 3, 6, and 12 months plus bivalent subtype c gp120 and mf59 adjuvant at 3, 6, and. Immunopotentiators in modern vaccines provides an indepth insight and overview of a number of most promising immunopotentiators in modern vaccines. The mechanism of action of mf59 an innately attractive. Fluad is a standarddose, threecomponent trivalent inactivated flu vaccine, manufactured by seqirus that contains an adjuvant. The mechanism of action of adjuvants is often poorly defined. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process.
Mf59 contains 2 nonionic surfactants, tween 80 and span 85. A strong influx of mononuclear cells in response to the injection of mf59 was shown by. Global medical affairs 10 may 2016 for scientific or medical use only. For a list of studies related to aluminum in vaccines, visit the aluminum page squalene mf59, as03, af03 weibel d, sturkenboom m, black, s, et al.
This statement reflected the ignorance on the mechanisms of action of most known adjuvants. We examined the effects of dppc supplier, buffer composition. It is also in arepannix and the new qpan for h5n1 influenza. The magnitude and duration of the antibody response to hepatitis b surface antigen antihbs induced by the hbv mf59 vaccine was compared with the same antigen combined with alum and with. Fluadmf59adjuvanted influenza vaccine in older adults. Mf59 has been shown to improve antibody responses to influenza, herpes simplex, cytomegalovirus, and hiv vaccines 9. Quotes mf59tm is a submicron oilinwater emulsion of a squalene, polyoxyethylene sorbitan monooleate and sorbitan trioleate. The initial work on the impact of mf59 on adjuvant and antigen distribution after im injection was followed by additional work, which further characterized the cellular populations at the site of injection and in the draining node. The amount of emulsion adjuvant required for an influenza vaccine can be reduced, thereby allowing more vaccines to be made from a given amount of emulsion, andor minimizing the amount of emulsion that has to be produced for a given number of vaccine doses. Since we have recently gained a number of insights on how. Seqirus presents favorable outcomes data for adjuvanted. Mf59 consists of an oil squaleneinwater nano emulision and is licensed in europe in influenza vaccines.
Mf59 adjuvanted influenza vaccine influenza prevention for vulnerable populations james a. Hvtn 100 is a phase 12, randomised controlled, doubleblind trial at six community research sites in south africa. It consists of aluminum hydroxide and monophosphoryl lipid a mpl. Baxter and novartis adjuvant of choice is called mf59, detailed in the article below as a powerful and highly toxic squalene compound.
The vaccine was developed primarily for use in elderly populations, but nonelderly individuals might also benefit. It is an adjuvant which helps to strengthen and lengthen the immune response to the vaccine. Overview of adjuvants that are part of euregistered vaccines. Mf59 has been shown to be safe and well tolerated in a number of clinical trials briones et al. For formulations containing mf59 adjuvant, vaccines were prepared by extemporaneous mixing, immediately before administration. Mf59 is added to the vaccine to make it more effective. Mf59 creates a local immunocompetent environment at the injection site. The purpose of the present studies was to directly address a question that has been asked of us on many occasions. Although adjuvants have been effective at increasing crossreactivity against viral strains that are not included in the vaccine, mansi said his company wants to combine the mf59 adjuvant with. Narcolepsy and adjuvanted pandemic influenza a h1n1 2009 vaccines. A handful of adjuvants are currently licensed for human vaccination table 3, and a number of new adjuvants have. In other words, adjuvants help vaccines work better. Aluminumcontaining adjuvants freunds adjuvantmechanism. Citrate buffer is also used in mf59 to stabilize ph.
Several studies done on human test subjects found mf59 to be a very safe immune adjuvant. They are used to elicit an early, high and longlasting immune response. Mf59 leads to recruitment of immune cells into the injection site. Highlights mf59 is a safe and well established vaccine adjuvant. Mf59, an oilinwater emulsion produced by microfluidization mf, was the first adjuvant to be used in a licensed seasonal influenza vaccine, 69. Fluad was approved in italy in 1997 and in the united states in november 2015. T1 adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine.
Subtype c alvachiv and bivalent subtype c gp120mf59 hiv. The development of liveattenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. A glimpse into the scary world of vaccine adjuvants. A cell culturederived mf59adjuvanted pandemic ah7n9. Mf59adjuvanted flu vaccine improves immune response in. Mf59 ingredients contains squalene, the main cause of gulf war syndrome. Mf59 is an oilinwater emulsion adjuvant that has been approved for use with seasonal influenza vaccines in several countries in europe since 1997. Gsks adjuvant, mlpas04 also identified as as03 in company statements and, like as01 and 2, contains mlp, or, in simple terms, squalene is also a powerful and literally poisonous auto immune.
Adjuvants taken from the latin, adjuvare, meaning to help are designed to improve poorly immunogenic vaccines. Adjuvants were originally described by ramon as substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone, thus encompassing a wide range of materials. Mf59 is a safe and effective vaccine adjuvant that has been used in a licensed seasonal influenza vaccine for 15 years. The composition of mf59 the oil used for mf59 is squalene, which is a naturally occurring triterpene hydrocarbon with a simple composition c 30 h 50. Optimizing manufacturing and composition of a tlr4. The droplet size of emulsion adjuvants has significant. This nanosuspension is a clinical vaccine adjuvant known as glaaf.
An adjuvant is an ingredient used in some vaccines that helps create a stronger immune response in people receiving the vaccine. It is manufactured using an eggbased process like most flu vaccines, and is formulated with the adjuvant mf59. Comparison of the safety, tolerability, and immunogenicity. New generation vaccine adjuvants derek t ohagan, novartis vaccines and diagnostics, inc. Furthermore, it is the successor of as03 which is a squalene based adjuvant approved for pandemic vaccine by the ema. When properly formulated, adjuvants can help to augment the breadth and magnitude of protective immune responses to vaccines. Squalene is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil hence its name, as squalus is a genus of sharks, although plant sources primarily vegetable oils are now used as well, including amaranth seed, rice bran, wheat germ, and olives. Adjuvants and alternative routes of administration towards.
The purpose of this chapter is to summarize our extensive experience with the oilinwater emulsion adjuvant mf59 and to emphasize to the reader that mf59 is no longer a research formulation, but a functional commercial adjuvant. Immunopotentiators in modern vaccines, second edition, provides indepth insights and overviews of the most successful adjuvants, those that have been included in licensed products, also covering the most promising technologies that have emerged in recent years. As03 for adjuvant system 03 is the trade name for a squalenebased immunologic adjuvant used in various vaccine products by glaxosmithkline gsk. Ep2377552a3 influenza vaccines with reduced amount of. Previously, we developed a nanosuspension consisting of the synthetic tlr4 ligand glucopyranosyl lipid adjuvant gla and dipalmitoyl phosphatidylcholine dppc.
Squalene is a natural organic compound originally obtained from. Sherri tenpenny, do nvic nih wants toxic adjuvant in flu vaccine mf59. Squalene, the oil in mf59, is a naturally occurring hydrocarbon extracted from livers of the dogshark, a small, nonendangered species. Key roles of adjuvants in modern vaccines nature medicine. The mf59 adjuvant has been used in several vaccines. Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Milan raska, jaroslav turanek, in mucosal immunology fourth edition, 2015. The adjuvants aluminum hydroxide and mf59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. Part of the methods in molecular medicine book series mimm. Vaccine ingredients childrens hospital of philadelphia. Vaccine adjuvants see also vaccines, therapeutic vaccines, dna vaccines and rna vaccines. In contrast to existing books on the subject it provides recent data on the critical mechanisms governing the activity of vaccine adjuvants and delivery systems. It may also lead to an increase in common side effects such as pain, swelling or redness at the injection site, slightly high temperature, headache, feeling generally unwell, shivering, or tiredness. It is significant that mf59 can overcome a defect in cd4 t cell help in exhibiting adjuvant effects on enhancing adaptive immunity to vaccination, suggesting a new paradigm of cd4independent adjuvant action mechanisms of mf59.
I know that many readers are concerned about the possible side effects of adjuvants. Mf59 has been used for 12 years in seasonal influenza vaccines in europe and is considered a safe adjuvant. Mf59 is a safe and effective adjuvant licensed to be included in influenza vaccines. The adjuvanted influenza vaccine fluad is composed of subunit influenza antigens combined with the mf59 adjuvant emulsion. It is used, for example, in gsks ah1n1 pandemic flu vaccine pandemrix. Mf59 a squalenebased emulsion was used to adjuvant influenza vaccine. These vaccines can conveniently be made by mixing i an oilinwater. Mf59 has also been tested with herpes simplex virus, hbv and hiv vaccine candidates dubensky and. Influenza is a major cause of respiratory disease leading to hospitalization in young children. Influenza vaccines with oilinwater emulsion adjuvants are known. However, seasonal trivalent influenza vaccines tivs have been shown to be ineffective and poorly immunogenic in this population. Adjuvants are formulated compounds, which when combined with vaccine antigens intensify the bodys immune response. Unlike most flu shots, fluad contains an adjuvant called mf59 and it is only for adults over 65. As03 and mf59adjuvanted influenza vaccines in children.
These vaccines, including tetanus and diphtheria, are the same vaccines frequently associated with adverse reactions. The chemical nature of adjuvants, their mode of action and their reactions side effect are highly variable in terms of how they affect the immune system and how. A key component of the mechanism of action of mf59 is cellular recruitment to the injection site. The adjuvant was first developed for influenza vaccination in the elderly, and later it was also found to be effective in young children. Mf59 adjuvant is an oilinwater emulsion, composed of squalene as the oil phase, stabilized with the surfactants polysorbate 80 and sorbitan trioleate, in citrate buffer. Adjuvant system 04 is a trade name for combination of adjuvants used in various vaccine product by glaxosmithkline gsk, in particular the fendrix hepatitis b vaccine. Fluad is designed specifically for people 65 years and older. Vaccine investigation and online information network.