Limits...
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

Differential kinetics of white blood cell populations enumerated by Coulter Counter at frequent time points following immunization with adjuvanted (red), unadjuvanted (green), or live (black) vaccines, or saline placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4562180&req=5

fig4: Differential kinetics of white blood cell populations enumerated by Coulter Counter at frequent time points following immunization with adjuvanted (red), unadjuvanted (green), or live (black) vaccines, or saline placebo.

Mentions: With these considerations in mind follow-on clinical trials involving over 200 participants will be carried out by BIOVACSAFE, for example, to further characterize a biomarker profile identified with an adjuvanted influenza vaccine (Figure 2). A particular feature of this follow-on trial is that not only will whole blood be collected for RNA extraction and transcriptomics, but also cells will be separated into monocyte and granulocyte fractions. This results from initial observations in the inpatient trials that lymphocyte subpopulations have marked kinetics with differences between adjuvanted and nonadjuvanted as well as live vaccines (Figure 4), with peaks and troughs that are sometimes concordant and at other times discordant. Although a typical systems vaccinology study of adjuvant effect may separate peripheral blood mononuclear cells (PBMCs) in an attempt to control for cellular kinetics, without these pilot data characterizing the exact time course, the wrong time points may be selected. In addition, granulocyte populations are generally overlooked as standard gradient centrifugation preparations will not easily isolate these cells, while data from the BIOVACSAFE intensive inpatient trials highlights significant activation of neutrophils by adjuvanted vaccines (Figure 4). By careful observations of cellular kinetics following adjuvanted or nonadjuvanted immunization, the BIOVACSAFE project has guided the design of trials which can better address the innate/inflammatory axis and focus on population such as neutrophils that are central actors in innate responses.


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

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

Differential kinetics of white blood cell populations enumerated by Coulter Counter at frequent time points following immunization with adjuvanted (red), unadjuvanted (green), or live (black) vaccines, or saline placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Differential kinetics of white blood cell populations enumerated by Coulter Counter at frequent time points following immunization with adjuvanted (red), unadjuvanted (green), or live (black) vaccines, or saline placebo.
Mentions: With these considerations in mind follow-on clinical trials involving over 200 participants will be carried out by BIOVACSAFE, for example, to further characterize a biomarker profile identified with an adjuvanted influenza vaccine (Figure 2). A particular feature of this follow-on trial is that not only will whole blood be collected for RNA extraction and transcriptomics, but also cells will be separated into monocyte and granulocyte fractions. This results from initial observations in the inpatient trials that lymphocyte subpopulations have marked kinetics with differences between adjuvanted and nonadjuvanted as well as live vaccines (Figure 4), with peaks and troughs that are sometimes concordant and at other times discordant. Although a typical systems vaccinology study of adjuvant effect may separate peripheral blood mononuclear cells (PBMCs) in an attempt to control for cellular kinetics, without these pilot data characterizing the exact time course, the wrong time points may be selected. In addition, granulocyte populations are generally overlooked as standard gradient centrifugation preparations will not easily isolate these cells, while data from the BIOVACSAFE intensive inpatient trials highlights significant activation of neutrophils by adjuvanted vaccines (Figure 4). By careful observations of cellular kinetics following adjuvanted or nonadjuvanted immunization, the BIOVACSAFE project has guided the design of trials which can better address the innate/inflammatory axis and focus on population such as neutrophils that are central actors in innate responses.

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