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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

(a) Day of onset for injection site reaction for five different vaccines plus saline placebo (blue), (b) schedule of sampling for systems vaccinology parameters during intensive inpatient studies.
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Related In: Results  -  Collection


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fig3: (a) Day of onset for injection site reaction for five different vaccines plus saline placebo (blue), (b) schedule of sampling for systems vaccinology parameters during intensive inpatient studies.

Mentions: Furthermore, in the typical systems vaccinology scenario, clinical samples are taken on days 0, 3, 5, and 7 and at weekly intervals thereafter to characterize immune responses in an outpatient setting, with the schedule being highly influenced by convenience of study organization, which misses very early time points when innate immune cells may be most active in setting the direction of subsequent immune response and reactogenicity. In contrast, the BIOVACSAFE clinical “training trials” were conducted in an inpatient setting in which diet, exercise, sleep, alcohol, and tobacco were strictly regulated to ensure minimal background variability that could interfere with subtle physiological events after immunization. This allowed very subtle changes to be detected as a signal in proteomic and transcriptomic readouts without background noise that would be expected in an outpatient setting. In addition, as most immediate inflammatory reactogenicity to vaccines or adjuvants occurs within the first few days (see Figure 3), this setting allowed samples to be taken extremely frequently in the first 72 hours, to permit unique characterization of very early innate immune activation (see Figure 3), both at the transcriptomic and the proteomic level (acute phase proteins, cytokines, and chemokines).


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

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

(a) Day of onset for injection site reaction for five different vaccines plus saline placebo (blue), (b) schedule of sampling for systems vaccinology parameters during intensive inpatient studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: (a) Day of onset for injection site reaction for five different vaccines plus saline placebo (blue), (b) schedule of sampling for systems vaccinology parameters during intensive inpatient studies.
Mentions: Furthermore, in the typical systems vaccinology scenario, clinical samples are taken on days 0, 3, 5, and 7 and at weekly intervals thereafter to characterize immune responses in an outpatient setting, with the schedule being highly influenced by convenience of study organization, which misses very early time points when innate immune cells may be most active in setting the direction of subsequent immune response and reactogenicity. In contrast, the BIOVACSAFE clinical “training trials” were conducted in an inpatient setting in which diet, exercise, sleep, alcohol, and tobacco were strictly regulated to ensure minimal background variability that could interfere with subtle physiological events after immunization. This allowed very subtle changes to be detected as a signal in proteomic and transcriptomic readouts without background noise that would be expected in an outpatient setting. In addition, as most immediate inflammatory reactogenicity to vaccines or adjuvants occurs within the first few days (see Figure 3), this setting allowed samples to be taken extremely frequently in the first 72 hours, to permit unique characterization of very early innate immune activation (see Figure 3), both at the transcriptomic and the proteomic level (acute phase proteins, cytokines, and chemokines).

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