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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

Illustration of need to identify a “safety boundary” on the sliding scale of adverse effects or biomarkers observed in response to “known to be safe” vaccines, immune agonists, and natural infection in animal models and human experimental medicine.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig6: Illustration of need to identify a “safety boundary” on the sliding scale of adverse effects or biomarkers observed in response to “known to be safe” vaccines, immune agonists, and natural infection in animal models and human experimental medicine.

Mentions: While a great deal can be achieved in human experimental medicine studies, and although it is increasingly accepted that animal models do not always reliably mimic the clinical experience, there are experiments that cannot ethically be conducted on humans; and rodents and rabbits remain the standard models for preclinical toxicology evaluation of adjuvanted vaccines. In addition, by studying only ethically acceptable and generally nonreactogenic vaccines in humans, it is difficult to know where the threshold of acceptability lies for any identified “biomarkers” (see Figure 6), in comparison, for example, with the inflammation induced by natural infection, which is assumed to be far greater than after immunisation. BIOVACSAFE will uniquely address this by integrating into the same data set human and animal data of transcriptomics and proteomics. Comparison will be made between human samples from the clinical trials and mice, rats, rabbits, and ferrets (blood, injection site, draining lymph nodes, spleen, liver, thymus, and bone marrow) immunized with the same adjuvanted and unadjuvanted vaccines or TLR-agonist positive controls, using a harmonized set of immune readouts (Table 2). Many bespoke assays have been created, particularly qPCR regents for ferret studies that are not commercially available, even though this species is an important influenza infection model. All these data will be integrated into a single integrated systems biology database for querying and analysis. Outputs may guide the use of appropriate preclinical toxicology models for novel adjuvants.


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

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

Illustration of need to identify a “safety boundary” on the sliding scale of adverse effects or biomarkers observed in response to “known to be safe” vaccines, immune agonists, and natural infection in animal models and human experimental medicine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Illustration of need to identify a “safety boundary” on the sliding scale of adverse effects or biomarkers observed in response to “known to be safe” vaccines, immune agonists, and natural infection in animal models and human experimental medicine.
Mentions: While a great deal can be achieved in human experimental medicine studies, and although it is increasingly accepted that animal models do not always reliably mimic the clinical experience, there are experiments that cannot ethically be conducted on humans; and rodents and rabbits remain the standard models for preclinical toxicology evaluation of adjuvanted vaccines. In addition, by studying only ethically acceptable and generally nonreactogenic vaccines in humans, it is difficult to know where the threshold of acceptability lies for any identified “biomarkers” (see Figure 6), in comparison, for example, with the inflammation induced by natural infection, which is assumed to be far greater than after immunisation. BIOVACSAFE will uniquely address this by integrating into the same data set human and animal data of transcriptomics and proteomics. Comparison will be made between human samples from the clinical trials and mice, rats, rabbits, and ferrets (blood, injection site, draining lymph nodes, spleen, liver, thymus, and bone marrow) immunized with the same adjuvanted and unadjuvanted vaccines or TLR-agonist positive controls, using a harmonized set of immune readouts (Table 2). Many bespoke assays have been created, particularly qPCR regents for ferret studies that are not commercially available, even though this species is an important influenza infection model. All these data will be integrated into a single integrated systems biology database for querying and analysis. Outputs may guide the use of appropriate preclinical toxicology models for novel adjuvants.

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