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Application of "Systems Vaccinology" to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines.

Lewis DJ, Lythgoe MP - J Immunol Res (2015)

Bottom Line: Advances in "omics" technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity.The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology.The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Centre, University of Surrey, Guildford GU2 7AX, UK.

ABSTRACT
Advances in "omics" technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing.

No MeSH data available.


Related in: MedlinePlus

Organization and sequence of head-to-head comparison of adjuvanted and unadjuvanted vaccines, with live vaccines in experimental medicine studies within the BIOVACSAFE project.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig2: Organization and sequence of head-to-head comparison of adjuvanted and unadjuvanted vaccines, with live vaccines in experimental medicine studies within the BIOVACSAFE project.

Mentions: The BIOVACSAFE project has significantly refined the previous approach of systems vaccinology in which a “training set” of data are generated from small clinical studies with around 15 healthy adult subjects per vaccine group, to identify putative correlations or biomarkers associated with a desired outcome (such as immunogenicity) which are then confirmed in larger “confirmatory studies” typically involving over 100 participants. For example, unlike previous efforts in which different vaccines are evaluated in separate trials (in which many variables may be different such as population, environment, and methodology), BIOVACSAFE has taken a highly structured approach to perform head-to-head comparisons in naive or immune populations using prototypic vaccines and adjuvants (see Figure 2) performed as separate groups within the same protocol at the same clinical site. Both adjuvanted (MF59C, AS04C, and alum) and unadjuvanted vaccines are compared head-to-head in primed (influenza and booster immunization with hepatitis B vaccines) and naive subjects (priming immunization with hepatitis B vaccine). Alongside these subunit adjuvanted vaccines, live viral vaccines were tested in naive (yellow fever) and immune (varicella) populations. This structure is unique to BIOVACSAFE and will allow biomarkers unique to each vaccine-target combination to be discriminated from more generalized biomarkers common to a number of vaccines or target populations.


Application of "Systems Vaccinology" to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines.

Lewis DJ, Lythgoe MP - J Immunol Res (2015)

Organization and sequence of head-to-head comparison of adjuvanted and unadjuvanted vaccines, with live vaccines in experimental medicine studies within the BIOVACSAFE project.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4562180&req=5

fig2: Organization and sequence of head-to-head comparison of adjuvanted and unadjuvanted vaccines, with live vaccines in experimental medicine studies within the BIOVACSAFE project.
Mentions: The BIOVACSAFE project has significantly refined the previous approach of systems vaccinology in which a “training set” of data are generated from small clinical studies with around 15 healthy adult subjects per vaccine group, to identify putative correlations or biomarkers associated with a desired outcome (such as immunogenicity) which are then confirmed in larger “confirmatory studies” typically involving over 100 participants. For example, unlike previous efforts in which different vaccines are evaluated in separate trials (in which many variables may be different such as population, environment, and methodology), BIOVACSAFE has taken a highly structured approach to perform head-to-head comparisons in naive or immune populations using prototypic vaccines and adjuvants (see Figure 2) performed as separate groups within the same protocol at the same clinical site. Both adjuvanted (MF59C, AS04C, and alum) and unadjuvanted vaccines are compared head-to-head in primed (influenza and booster immunization with hepatitis B vaccines) and naive subjects (priming immunization with hepatitis B vaccine). Alongside these subunit adjuvanted vaccines, live viral vaccines were tested in naive (yellow fever) and immune (varicella) populations. This structure is unique to BIOVACSAFE and will allow biomarkers unique to each vaccine-target combination to be discriminated from more generalized biomarkers common to a number of vaccines or target populations.

Bottom Line: Advances in "omics" technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity.The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology.The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Centre, University of Surrey, Guildford GU2 7AX, UK.

ABSTRACT
Advances in "omics" technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing.

No MeSH data available.


Related in: MedlinePlus