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Vaccine Adjuvants: from 1920 to 2015 and Beyond.

Pasquale AD, Preiss S, Silva FT, Garçon N - Vaccines (Basel) (2015)

Bottom Line: While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit.Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable.Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects.

View Article: PubMed Central - PubMed

Affiliation: GSK Vaccines, Avenue Fleming, 1300 Wavre, Belgium. alberta.di-pasquale@gsk.com.

ABSTRACT
The concept of stimulating the body's immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines.

No MeSH data available.


Related in: MedlinePlus

Licensed vaccines with or without adjuvant.
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vaccines-03-00320-f003: Licensed vaccines with or without adjuvant.

Mentions: Like many important medical breakthroughs, the discovery of the immune-enhancing effects of adding an adjuvant to a vaccine was serendipitous. Gaston Ramon, a French veterinarian, observed that the yield of tetanus and diphtheria anti-sera from horses was higher from animals that had developed an abscess at the injection site [24]. By injecting starch, breadcrumbs or tapioca, he induced sterile abscesses at the site of injection with inactivated toxin, and thus was able to increase anti-sera production, confirming the hypothesis that substances able to induce local inflammation at the injection site were also able to enhance anti-sera yield. Around the same time, Alexander Glenny working with colleagues in London discovered the immune-enhancing effects of aluminum salts. Aluminum was first used in human vaccines in 1932 and was the only adjuvant in use in licensed vaccines for approximately 70 years. Despite its extensive and continuous use, the immune mechanism of action of aluminum remains incompletely understood [25]. Aluminum adjuvants act primarily to increase antibody production and are therefore suitable for vaccines targeting pathogens killed primarily by antibodies. Aluminum-adjuvanted vaccines have not been successful in preventing infection due to intracellular pathogens [25]. Another early adjuvant attempt was a mineral oil-in-water emulsion (Freund’s incomplete adjuvant) which was considered too reactogenic for continued use in humans. Adjuvants have been used for more than 90 years and are currently components of more than 30 licensed vaccines from different manufacturers (Figure 3).


Vaccine Adjuvants: from 1920 to 2015 and Beyond.

Pasquale AD, Preiss S, Silva FT, Garçon N - Vaccines (Basel) (2015)

Licensed vaccines with or without adjuvant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494348&req=5

vaccines-03-00320-f003: Licensed vaccines with or without adjuvant.
Mentions: Like many important medical breakthroughs, the discovery of the immune-enhancing effects of adding an adjuvant to a vaccine was serendipitous. Gaston Ramon, a French veterinarian, observed that the yield of tetanus and diphtheria anti-sera from horses was higher from animals that had developed an abscess at the injection site [24]. By injecting starch, breadcrumbs or tapioca, he induced sterile abscesses at the site of injection with inactivated toxin, and thus was able to increase anti-sera production, confirming the hypothesis that substances able to induce local inflammation at the injection site were also able to enhance anti-sera yield. Around the same time, Alexander Glenny working with colleagues in London discovered the immune-enhancing effects of aluminum salts. Aluminum was first used in human vaccines in 1932 and was the only adjuvant in use in licensed vaccines for approximately 70 years. Despite its extensive and continuous use, the immune mechanism of action of aluminum remains incompletely understood [25]. Aluminum adjuvants act primarily to increase antibody production and are therefore suitable for vaccines targeting pathogens killed primarily by antibodies. Aluminum-adjuvanted vaccines have not been successful in preventing infection due to intracellular pathogens [25]. Another early adjuvant attempt was a mineral oil-in-water emulsion (Freund’s incomplete adjuvant) which was considered too reactogenic for continued use in humans. Adjuvants have been used for more than 90 years and are currently components of more than 30 licensed vaccines from different manufacturers (Figure 3).

Bottom Line: While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit.Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable.Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects.

View Article: PubMed Central - PubMed

Affiliation: GSK Vaccines, Avenue Fleming, 1300 Wavre, Belgium. alberta.di-pasquale@gsk.com.

ABSTRACT
The concept of stimulating the body's immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines.

No MeSH data available.


Related in: MedlinePlus