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Adjuvants in the Driver's Seat: How Magnitude, Type, Fine Specificity and Longevity of Immune Responses Are Driven by Distinct Classes of Immune Potentiators.

Bergmann-Leitner ES, Leitner WW - Vaccines (Basel) (2014)

Bottom Line: From here, the antigen is slowly released and provided to immune cells over an extended period of time.The identification of Pathogen-Associated Molecular Patterns (PAMPs) has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants.A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

View Article: PubMed Central - PubMed

Affiliation: US Military Malaria Research Program, Malaria Vaccine Branch, 503 Robert Grant Ave, 3W65, Silver Spring, MD 20910, USA. elke.bergmannleitner@us.army.mil.

ABSTRACT
The mechanism by which vaccine adjuvants enhance immune responses has historically been considered to be the creation of an antigen depot. From here, the antigen is slowly released and provided to immune cells over an extended period of time. This "depot" was formed by associating the antigen with substances able to persist at the injection site, such as aluminum salts or emulsions. The identification of Pathogen-Associated Molecular Patterns (PAMPs) has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants. This review focuses on the mode of action of different adjuvant classes in regards to the stimulation of specific immune cell subsets, the biasing of immune responses towards cellular or humoral immune response, the ability to mediate epitope spreading and the induction of persistent immunological memory. A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

No MeSH data available.


Related in: MedlinePlus

This figure provides a highly simplified overview of Pattern Recognition Receptors (PRR) and the molecular events triggered by the recognition of Pathogen Associated Molecular Patterns (PAMPs) on/inside pathogens. Immune cells as well as many somatic cells express soluble extracellular (not shown), cell surface, and intracellular sentinels for detecting infections. These receptors are specific for distinct classes of pathogen (i.e., bacteria, viruses, fungi, parasites) and are strategically positioned: e.g., receptors that recognize surface components of bacteria such as LPS or LTA are present extracellularly or as soluble molecules (e.g., Mannan-Binding Protein, MBP); receptors for viral RNA are located inside the cell (cytoplasm and phagosome). Binding of PRR to their specific PAMP activates a signaling cascade which relies on common adapter molecules (e.g., MyD88, TRIF), and results in the downstream translation of numerous gene products. Adjuvants emulate these interactions between pathogen and immune system.
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vaccines-02-00252-f001: This figure provides a highly simplified overview of Pattern Recognition Receptors (PRR) and the molecular events triggered by the recognition of Pathogen Associated Molecular Patterns (PAMPs) on/inside pathogens. Immune cells as well as many somatic cells express soluble extracellular (not shown), cell surface, and intracellular sentinels for detecting infections. These receptors are specific for distinct classes of pathogen (i.e., bacteria, viruses, fungi, parasites) and are strategically positioned: e.g., receptors that recognize surface components of bacteria such as LPS or LTA are present extracellularly or as soluble molecules (e.g., Mannan-Binding Protein, MBP); receptors for viral RNA are located inside the cell (cytoplasm and phagosome). Binding of PRR to their specific PAMP activates a signaling cascade which relies on common adapter molecules (e.g., MyD88, TRIF), and results in the downstream translation of numerous gene products. Adjuvants emulate these interactions between pathogen and immune system.

Mentions: For the last couple of decades the trend in vaccinology has been towards simple and more defined vaccines, which are based on select pathogen-derived antigens. Compared to vaccines, which are based on attenuated pathogens, those that use a limited number of pathogen-derived antigens tend to be characterized by a more favorable safety profile and a more straight-forward manufacturing process. They are also based on an improved understanding of immune responses against the pathogens and the knowledge that immune responses against some antigens are more desirable than responses against other antigens such as those associated with immune escape or other undesirable features including cross-reactivity with host antigens. However, using “clean” recombinant antigens removes PAMPs. These conserved, pathogen-derived molecules are recognized by germ-line encoded, evolutionarily conserved innate immune receptors, pattern recognition receptors (PRR, reviewed in [21]), whose presence and activity can transform weakly or non-immunogenic antigens into immunogens capable of triggering T and B cell responses (Figure 1). The inadequate immunogenicity of recombinant proteins as well as carbohydrate antigens has been the driving force behind the search for compounds to endow them with the immunostimulatory capabilities of microbial pathogens, and thus adjuvant discovery. Adjuvant research, however, is more than the identification of novel immunostimulatory molecules. It also includes the proper formulation of the vaccine to achieve maximal immunogenicity.


Adjuvants in the Driver's Seat: How Magnitude, Type, Fine Specificity and Longevity of Immune Responses Are Driven by Distinct Classes of Immune Potentiators.

Bergmann-Leitner ES, Leitner WW - Vaccines (Basel) (2014)

This figure provides a highly simplified overview of Pattern Recognition Receptors (PRR) and the molecular events triggered by the recognition of Pathogen Associated Molecular Patterns (PAMPs) on/inside pathogens. Immune cells as well as many somatic cells express soluble extracellular (not shown), cell surface, and intracellular sentinels for detecting infections. These receptors are specific for distinct classes of pathogen (i.e., bacteria, viruses, fungi, parasites) and are strategically positioned: e.g., receptors that recognize surface components of bacteria such as LPS or LTA are present extracellularly or as soluble molecules (e.g., Mannan-Binding Protein, MBP); receptors for viral RNA are located inside the cell (cytoplasm and phagosome). Binding of PRR to their specific PAMP activates a signaling cascade which relies on common adapter molecules (e.g., MyD88, TRIF), and results in the downstream translation of numerous gene products. Adjuvants emulate these interactions between pathogen and immune system.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494256&req=5

vaccines-02-00252-f001: This figure provides a highly simplified overview of Pattern Recognition Receptors (PRR) and the molecular events triggered by the recognition of Pathogen Associated Molecular Patterns (PAMPs) on/inside pathogens. Immune cells as well as many somatic cells express soluble extracellular (not shown), cell surface, and intracellular sentinels for detecting infections. These receptors are specific for distinct classes of pathogen (i.e., bacteria, viruses, fungi, parasites) and are strategically positioned: e.g., receptors that recognize surface components of bacteria such as LPS or LTA are present extracellularly or as soluble molecules (e.g., Mannan-Binding Protein, MBP); receptors for viral RNA are located inside the cell (cytoplasm and phagosome). Binding of PRR to their specific PAMP activates a signaling cascade which relies on common adapter molecules (e.g., MyD88, TRIF), and results in the downstream translation of numerous gene products. Adjuvants emulate these interactions between pathogen and immune system.
Mentions: For the last couple of decades the trend in vaccinology has been towards simple and more defined vaccines, which are based on select pathogen-derived antigens. Compared to vaccines, which are based on attenuated pathogens, those that use a limited number of pathogen-derived antigens tend to be characterized by a more favorable safety profile and a more straight-forward manufacturing process. They are also based on an improved understanding of immune responses against the pathogens and the knowledge that immune responses against some antigens are more desirable than responses against other antigens such as those associated with immune escape or other undesirable features including cross-reactivity with host antigens. However, using “clean” recombinant antigens removes PAMPs. These conserved, pathogen-derived molecules are recognized by germ-line encoded, evolutionarily conserved innate immune receptors, pattern recognition receptors (PRR, reviewed in [21]), whose presence and activity can transform weakly or non-immunogenic antigens into immunogens capable of triggering T and B cell responses (Figure 1). The inadequate immunogenicity of recombinant proteins as well as carbohydrate antigens has been the driving force behind the search for compounds to endow them with the immunostimulatory capabilities of microbial pathogens, and thus adjuvant discovery. Adjuvant research, however, is more than the identification of novel immunostimulatory molecules. It also includes the proper formulation of the vaccine to achieve maximal immunogenicity.

Bottom Line: From here, the antigen is slowly released and provided to immune cells over an extended period of time.The identification of Pathogen-Associated Molecular Patterns (PAMPs) has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants.A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

View Article: PubMed Central - PubMed

Affiliation: US Military Malaria Research Program, Malaria Vaccine Branch, 503 Robert Grant Ave, 3W65, Silver Spring, MD 20910, USA. elke.bergmannleitner@us.army.mil.

ABSTRACT
The mechanism by which vaccine adjuvants enhance immune responses has historically been considered to be the creation of an antigen depot. From here, the antigen is slowly released and provided to immune cells over an extended period of time. This "depot" was formed by associating the antigen with substances able to persist at the injection site, such as aluminum salts or emulsions. The identification of Pathogen-Associated Molecular Patterns (PAMPs) has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants. This review focuses on the mode of action of different adjuvant classes in regards to the stimulation of specific immune cell subsets, the biasing of immune responses towards cellular or humoral immune response, the ability to mediate epitope spreading and the induction of persistent immunological memory. A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

No MeSH data available.


Related in: MedlinePlus