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Eberhard Hildt - One of the best experts on this subject based on the ideXlab platform.
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Zusammensetzung und Wirkmechanismen von Adjuvanzien in zugelassenen viralen Impfstoffen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2019Co-Authors: Ralf Wagner, Eberhard HildtAbstract:The immunogenicity and efficacy of vaccines is largely governed by nature and the amount of antigen(s) included. Specific immune-stimulating substances, so-called Adjuvants, are added to vaccine formulations to enhance and modulate the induced immune response. Adjuvants are very different in their physicochemical nature and are primarily characterized by their immune-enhancing effects. In this report, Adjuvants that are components of vaccines licensed in the EU will be presented and their mode of action will be discussed. Aluminum salts have been used for almost a century as vaccine Adjuvants. In recent years numerous novel immune-stimulating substances have been developed and integrated into licensed human vaccines. These novel Adjuvants are not only intended to generally increase the vaccine-induced antibody titers, but are also aimed at modulating and triggering a specific immune response. The search for innovative Adjuvants was considerably stimulated during development of pandemic influenza vaccines. By using squalene-containing oil-in-water Adjuvants (namely AS03 and MF59), pandemic influenza vaccines were developed that were efficacious despite a significant reduction of the antigen content. The development of novel Adjuvants is a highly dynamic and essential area in modern vaccine design. Some years ago, vaccines for prevention of HPV-induced cervix carcinoma and hepatitis B were licensed that contained the toll-like receptor 4 agonist 3‑O-desacyl-monophosphoryl lipid A (MPL), a detoxified LPS version, as the adjuvant. Quite recently, a herpes zoster vaccine was licensed in Europe with a combination of MPL and the saponin QS21 as adjuvant. This combination of immune enhancers is also used in the formulations of the same manufacturer’s malaria and hepatitis B vaccine.ZusammenfassungDie Immunogenität und Wirksamkeit von Impfstoffen werden in erster Linie von den enthaltenen Antigenen bestimmt. Die induzierte Immunantwort kann jedoch durch Zugabe von Wirkverstärkern in der Impfstoffformulierung, sog. Adjuvanzien, maßgeblich beeinflusst und gesteuert werden. Adjuvanzien sind stofflich sehr divers und durch ihren die Immunantwort verstärkenden Effekt gekennzeichnet. In diesem Beitrag werden Adjuvanzien, die Teil in der EU zugelassener Impfstoffe sind, vorgestellt und ihre immunologischen Wirkmechanismen beschrieben. Aluminiumsalze werden bereits seit 100 Jahren als Adjuvans eingesetzt. In jüngster Zeit wurde eine ganze Reihe neuartiger Adjuvanzien entwickelt und in zugelassene Impfstoffprodukte integriert. Viele der neuen Adjuvanzien führen nicht allein zu einer Erhöhung der impfstoffinduzierten Antikörpertiter, sondern zielen auch darauf ab, die Immunantwort in eine bestimmte Richtung zu lenken und gezielt zu modulieren. Die Suche nach innovativen Wirkverstärkern wurde wesentlich vorangetrieben bei der Entwicklung pandemischer Influenzaimpfstoffe. Durch Verwendung neuartiger Öl-in-Wasser-Emulsionen (Adjuvanzien MF 59 und AS03) gelang es, Pandemieimpfstoffe zu entwickeln, die trotz deutlich verringertem Antigengehalt wirksam sind. Die Entwicklung neuer Adjuvanzien ist ein sehr dynamischer und zentraler Aspekt des Impfstoffdesigns: Vor einigen Jahren wurden Impfstoffe gegen das HPV-induzierte humane Zervixkarzinom und Hepatitis B zugelassen, die den Toll-like-Rezeptor-4-Agonisten MPL (3-O-Desacyl-monophosphoryl Lipid A) als Adjuvansbestandteil enthalten. Jüngst wurde in Europa ein Impfstoff gegen Herpes Zoster zugelassen, der als Adjuvans eine Kombination aus MPL und dem Saponin QS21 enthält, die auch im Malaria- und im Hepatitis-B-Impfstoff des Herstellers zur Anwendung kommen.
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Zusammensetzung und Wirkmechanismen von Adjuvanzien in zugelassenen viralen Impfstoffen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2019Co-Authors: Ralf Wagner, Eberhard HildtAbstract:The immunogenicity and efficacy of vaccines is largely governed by nature and the amount of antigen(s) included. Specific immune-stimulating substances, so-called Adjuvants, are added to vaccine formulations to enhance and modulate the induced immune response. Adjuvants are very different in their physicochemical nature and are primarily characterized by their immune-enhancing effects. In this report, Adjuvants that are components of vaccines licensed in the EU will be presented and their mode of action will be discussed. Aluminum salts have been used for almost a century as vaccine Adjuvants. In recent years numerous novel immune-stimulating substances have been developed and integrated into licensed human vaccines. These novel Adjuvants are not only intended to generally increase the vaccine-induced antibody titers, but are also aimed at modulating and triggering a specific immune response. The search for innovative Adjuvants was considerably stimulated during development of pandemic influenza vaccines. By using squalene-containing oil-in-water Adjuvants (namely AS03 and MF59), pandemic influenza vaccines were developed that were efficacious despite a significant reduction of the antigen content. The development of novel Adjuvants is a highly dynamic and essential area in modern vaccine design. Some years ago, vaccines for prevention of HPV-induced cervix carcinoma and hepatitis B were licensed that contained the toll-like receptor 4 agonist 3‑O-desacyl-monophosphoryl lipid A (MPL), a detoxified LPS version, as the adjuvant. Quite recently, a herpes zoster vaccine was licensed in Europe with a combination of MPL and the saponin QS21 as adjuvant. This combination of immune enhancers is also used in the formulations of the same manufacturer’s malaria and hepatitis B vaccine. Die Immunogenität und Wirksamkeit von Impfstoffen werden in erster Linie von den enthaltenen Antigenen bestimmt. Die induzierte Immunantwort kann jedoch durch Zugabe von Wirkverstärkern in der Impfstoffformulierung, sog. Adjuvanzien, maßgeblich beeinflusst und gesteuert werden. Adjuvanzien sind stofflich sehr divers und durch ihren die Immunantwort verstärkenden Effekt gekennzeichnet. In diesem Beitrag werden Adjuvanzien, die Teil in der EU zugelassener Impfstoffe sind, vorgestellt und ihre immunologischen Wirkmechanismen beschrieben. Aluminiumsalze werden bereits seit 100 Jahren als Adjuvans eingesetzt. In jüngster Zeit wurde eine ganze Reihe neuartiger Adjuvanzien entwickelt und in zugelassene Impfstoffprodukte integriert. Viele der neuen Adjuvanzien führen nicht allein zu einer Erhöhung der impfstoffinduzierten Antikörpertiter, sondern zielen auch darauf ab, die Immunantwort in eine bestimmte Richtung zu lenken und gezielt zu modulieren. Die Suche nach innovativen Wirkverstärkern wurde wesentlich vorangetrieben bei der Entwicklung pandemischer Influenzaimpfstoffe. Durch Verwendung neuartiger Öl-in-Wasser-Emulsionen (Adjuvanzien MF 59 und AS03) gelang es, Pandemieimpfstoffe zu entwickeln, die trotz deutlich verringertem Antigengehalt wirksam sind. Die Entwicklung neuer Adjuvanzien ist ein sehr dynamischer und zentraler Aspekt des Impfstoffdesigns: Vor einigen Jahren wurden Impfstoffe gegen das HPV-induzierte humane Zervixkarzinom und Hepatitis B zugelassen, die den Toll-like-Rezeptor-4-Agonisten MPL (3-O-Desacyl-monophosphoryl Lipid A) als Adjuvansbestandteil enthalten. Jüngst wurde in Europa ein Impfstoff gegen Herpes Zoster zugelassen, der als Adjuvans eine Kombination aus MPL und dem Saponin QS21 enthält, die auch im Malaria- und im Hepatitis-B-Impfstoff des Herstellers zur Anwendung kommen.
Yehuda Shoenfeld - One of the best experts on this subject based on the ideXlab platform.
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autoimmune inflammatory syndrome induced by Adjuvants asia 2013 unveiling the pathogenic clinical and diagnostic aspects
Journal of Autoimmunity, 2013Co-Authors: Carlo Perricone, Serena Colafrancesco, Alessandra Soriano, Roei David Mazor, Nancy Agmonlevin, Yehuda ShoenfeldAbstract:In 2011 a new syndrome termed ‘ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants’ was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other Adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with postvaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different Adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the
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Autoimmune/inflammatory syndrome induced by Adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects
Journal of Autoimmunity, 2013Co-Authors: Carlo Perricone, Serena Colafrancesco, Alessandra Soriano, Roei David Mazor, Nancy Agmon-levin, Yehuda ShoenfeldAbstract:In 2011 a new syndrome termed ‘ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants’ was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other Adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with postvaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different Adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the
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Adjuvants and autoimmunity
Lupus, 2009Co-Authors: Eitan Israeli, Nancy Agmonlevin, M Blank, Yehuda ShoenfeldAbstract:Some Adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer Adjuvants, several new Adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many Adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, Adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as ‘the adjuvant diseases’. The debatable question of sili...
Ralf Wagner - One of the best experts on this subject based on the ideXlab platform.
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Zusammensetzung und Wirkmechanismen von Adjuvanzien in zugelassenen viralen Impfstoffen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2019Co-Authors: Ralf Wagner, Eberhard HildtAbstract:The immunogenicity and efficacy of vaccines is largely governed by nature and the amount of antigen(s) included. Specific immune-stimulating substances, so-called Adjuvants, are added to vaccine formulations to enhance and modulate the induced immune response. Adjuvants are very different in their physicochemical nature and are primarily characterized by their immune-enhancing effects. In this report, Adjuvants that are components of vaccines licensed in the EU will be presented and their mode of action will be discussed. Aluminum salts have been used for almost a century as vaccine Adjuvants. In recent years numerous novel immune-stimulating substances have been developed and integrated into licensed human vaccines. These novel Adjuvants are not only intended to generally increase the vaccine-induced antibody titers, but are also aimed at modulating and triggering a specific immune response. The search for innovative Adjuvants was considerably stimulated during development of pandemic influenza vaccines. By using squalene-containing oil-in-water Adjuvants (namely AS03 and MF59), pandemic influenza vaccines were developed that were efficacious despite a significant reduction of the antigen content. The development of novel Adjuvants is a highly dynamic and essential area in modern vaccine design. Some years ago, vaccines for prevention of HPV-induced cervix carcinoma and hepatitis B were licensed that contained the toll-like receptor 4 agonist 3‑O-desacyl-monophosphoryl lipid A (MPL), a detoxified LPS version, as the adjuvant. Quite recently, a herpes zoster vaccine was licensed in Europe with a combination of MPL and the saponin QS21 as adjuvant. This combination of immune enhancers is also used in the formulations of the same manufacturer’s malaria and hepatitis B vaccine.ZusammenfassungDie Immunogenität und Wirksamkeit von Impfstoffen werden in erster Linie von den enthaltenen Antigenen bestimmt. Die induzierte Immunantwort kann jedoch durch Zugabe von Wirkverstärkern in der Impfstoffformulierung, sog. Adjuvanzien, maßgeblich beeinflusst und gesteuert werden. Adjuvanzien sind stofflich sehr divers und durch ihren die Immunantwort verstärkenden Effekt gekennzeichnet. In diesem Beitrag werden Adjuvanzien, die Teil in der EU zugelassener Impfstoffe sind, vorgestellt und ihre immunologischen Wirkmechanismen beschrieben. Aluminiumsalze werden bereits seit 100 Jahren als Adjuvans eingesetzt. In jüngster Zeit wurde eine ganze Reihe neuartiger Adjuvanzien entwickelt und in zugelassene Impfstoffprodukte integriert. Viele der neuen Adjuvanzien führen nicht allein zu einer Erhöhung der impfstoffinduzierten Antikörpertiter, sondern zielen auch darauf ab, die Immunantwort in eine bestimmte Richtung zu lenken und gezielt zu modulieren. Die Suche nach innovativen Wirkverstärkern wurde wesentlich vorangetrieben bei der Entwicklung pandemischer Influenzaimpfstoffe. Durch Verwendung neuartiger Öl-in-Wasser-Emulsionen (Adjuvanzien MF 59 und AS03) gelang es, Pandemieimpfstoffe zu entwickeln, die trotz deutlich verringertem Antigengehalt wirksam sind. Die Entwicklung neuer Adjuvanzien ist ein sehr dynamischer und zentraler Aspekt des Impfstoffdesigns: Vor einigen Jahren wurden Impfstoffe gegen das HPV-induzierte humane Zervixkarzinom und Hepatitis B zugelassen, die den Toll-like-Rezeptor-4-Agonisten MPL (3-O-Desacyl-monophosphoryl Lipid A) als Adjuvansbestandteil enthalten. Jüngst wurde in Europa ein Impfstoff gegen Herpes Zoster zugelassen, der als Adjuvans eine Kombination aus MPL und dem Saponin QS21 enthält, die auch im Malaria- und im Hepatitis-B-Impfstoff des Herstellers zur Anwendung kommen.
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Zusammensetzung und Wirkmechanismen von Adjuvanzien in zugelassenen viralen Impfstoffen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 2019Co-Authors: Ralf Wagner, Eberhard HildtAbstract:The immunogenicity and efficacy of vaccines is largely governed by nature and the amount of antigen(s) included. Specific immune-stimulating substances, so-called Adjuvants, are added to vaccine formulations to enhance and modulate the induced immune response. Adjuvants are very different in their physicochemical nature and are primarily characterized by their immune-enhancing effects. In this report, Adjuvants that are components of vaccines licensed in the EU will be presented and their mode of action will be discussed. Aluminum salts have been used for almost a century as vaccine Adjuvants. In recent years numerous novel immune-stimulating substances have been developed and integrated into licensed human vaccines. These novel Adjuvants are not only intended to generally increase the vaccine-induced antibody titers, but are also aimed at modulating and triggering a specific immune response. The search for innovative Adjuvants was considerably stimulated during development of pandemic influenza vaccines. By using squalene-containing oil-in-water Adjuvants (namely AS03 and MF59), pandemic influenza vaccines were developed that were efficacious despite a significant reduction of the antigen content. The development of novel Adjuvants is a highly dynamic and essential area in modern vaccine design. Some years ago, vaccines for prevention of HPV-induced cervix carcinoma and hepatitis B were licensed that contained the toll-like receptor 4 agonist 3‑O-desacyl-monophosphoryl lipid A (MPL), a detoxified LPS version, as the adjuvant. Quite recently, a herpes zoster vaccine was licensed in Europe with a combination of MPL and the saponin QS21 as adjuvant. This combination of immune enhancers is also used in the formulations of the same manufacturer’s malaria and hepatitis B vaccine. Die Immunogenität und Wirksamkeit von Impfstoffen werden in erster Linie von den enthaltenen Antigenen bestimmt. Die induzierte Immunantwort kann jedoch durch Zugabe von Wirkverstärkern in der Impfstoffformulierung, sog. Adjuvanzien, maßgeblich beeinflusst und gesteuert werden. Adjuvanzien sind stofflich sehr divers und durch ihren die Immunantwort verstärkenden Effekt gekennzeichnet. In diesem Beitrag werden Adjuvanzien, die Teil in der EU zugelassener Impfstoffe sind, vorgestellt und ihre immunologischen Wirkmechanismen beschrieben. Aluminiumsalze werden bereits seit 100 Jahren als Adjuvans eingesetzt. In jüngster Zeit wurde eine ganze Reihe neuartiger Adjuvanzien entwickelt und in zugelassene Impfstoffprodukte integriert. Viele der neuen Adjuvanzien führen nicht allein zu einer Erhöhung der impfstoffinduzierten Antikörpertiter, sondern zielen auch darauf ab, die Immunantwort in eine bestimmte Richtung zu lenken und gezielt zu modulieren. Die Suche nach innovativen Wirkverstärkern wurde wesentlich vorangetrieben bei der Entwicklung pandemischer Influenzaimpfstoffe. Durch Verwendung neuartiger Öl-in-Wasser-Emulsionen (Adjuvanzien MF 59 und AS03) gelang es, Pandemieimpfstoffe zu entwickeln, die trotz deutlich verringertem Antigengehalt wirksam sind. Die Entwicklung neuer Adjuvanzien ist ein sehr dynamischer und zentraler Aspekt des Impfstoffdesigns: Vor einigen Jahren wurden Impfstoffe gegen das HPV-induzierte humane Zervixkarzinom und Hepatitis B zugelassen, die den Toll-like-Rezeptor-4-Agonisten MPL (3-O-Desacyl-monophosphoryl Lipid A) als Adjuvansbestandteil enthalten. Jüngst wurde in Europa ein Impfstoff gegen Herpes Zoster zugelassen, der als Adjuvans eine Kombination aus MPL und dem Saponin QS21 enthält, die auch im Malaria- und im Hepatitis-B-Impfstoff des Herstellers zur Anwendung kommen.
Rajesh K. Gupta - One of the best experts on this subject based on the ideXlab platform.
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aluminum compounds as vaccine Adjuvants
Advanced Drug Delivery Reviews, 1998Co-Authors: Rajesh K. GuptaAbstract:Abstract Aluminum compounds are the only Adjuvants used widely with routine human vaccines and are the most common Adjuvants in veterinary vaccines also. Though there has been a search for alternate Adjuvants, aluminum Adjuvants will continue to be used for many years due to their good track record of safety, low cost and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminum Adjuvants formulated under optimal conditions are the Adjuvants of choice. It is important to select carefully the type of aluminum adjuvant and optimize the conditions of adsorption for every antigen since this process is dependent upon the physico-chemical characteristics of both the antigens and aluminum Adjuvants. Adsorption of antigens onto aluminum compounds depends heavily on electrostatic forces between adjuvant and antigen. Two commonly used aluminum Adjuvants, aluminum hydroxide and aluminum phosphate have opposite charge at a neutral pH. The mechanism of adjuvanticity of aluminum compounds includes formation of a depot; efficient uptake of aluminum adsorbed antigen particles by antigen presenting cells due their particulate nature and optimal size (
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Adjuvants for human vaccines-current status, problems and future prospects
Vaccine, 1995Co-Authors: Rajesh K. Gupta, George R. SiberAbstract:Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, Adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require Adjuvants to evoke the immune response. With the use of Adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of Adjuvants for human vaccines. The biggest issue with the use of Adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of Adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of Adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum Adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common Adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative Adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines. © 1995.
George R. Siber - One of the best experts on this subject based on the ideXlab platform.
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Adjuvants for human vaccines—current status, problems and future prospects☆
Vaccine, 1995Co-Authors: Rajesh Gupta, George R. SiberAbstract:Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, Adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require Adjuvants to evoke the immune response. With the use of Adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of Adjuvants for human vaccines. The biggest issue with the use of Adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of Adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of Adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum Adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common Adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative Adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines.
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Adjuvants for human vaccines-current status, problems and future prospects
Vaccine, 1995Co-Authors: Rajesh K. Gupta, George R. SiberAbstract:Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, Adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require Adjuvants to evoke the immune response. With the use of Adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of Adjuvants for human vaccines. The biggest issue with the use of Adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of Adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of Adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum Adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common Adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative Adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines. © 1995.
