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Hand-in-hand work between the Sponsor and the BA lab : a 5-year journey feedback toward the successful use of an IFN-γ ELISpot method supporting the clinical development of a new vaccine candidate

Developing reliable methods for monitoring cellular responses to a vaccine is akin to an obstacle course all along the process, from bedside - drawing blood from the patient - to bench - analyzing these samples for their immunogenicity. Understanding the context of use of the assay, including indication, expected magnitude of responses, injection regimen (prime +/- boost), sampling schedule, end use of data (dose-finding, correlates of protection, surrogate marker, statistical analysis…) determine the design and the level of validation of the assay. 

We illustrate here how, during the clinical development of OVX836, an innovative universal flu vaccine candidate, Osivax, as the Sponsor, and Active Biomarkers, as the bioanalytical lab, have worked hand-in-hand to develop an IFN-g ELISpot method and improve its robustness throughout the clinical development of the vaccine. We will showcase the steps allowing to move forward from an exploratory endpoint in phase 1 – which aims at exploring the kinetics of responses to the vaccine in relation with the route of administration and the dose of the vaccine – to a primary endpoint in more advanced phase 2 clinical studies. We show how sample integrity, strict control of the critical reagents, and of the method along clinical sample analysis are the key elements that will determine the reliability and comparability of data across clinical studies. 

Comprehensive Phenotyping of Immune Cell Subsets

The development of immuno-modulating therapies requires a comprehensive monitoring of patients' immune cell subsets in order to characterize the impact of the drugs on the immune system.

IMMUNE CELL MONITORING INCLUDES
• Measuring the frequency and absolute number of specific immune cell subsets in biological fluids (i.e. peripheral blood, CSF, etc.) and tissues.
• Monitoring changes in the expression of specific intra-cellular or cell-surface markers by immune cells.
• Enumerating antigen specific humoral and cellular immune responses (antibody secreting B cells, CD4 and/or CD8 T cells, etc.).
• Analyzing changes in the functional properties of different cell subsets : cytotoxicity, proliferation, secretion patterns of soluble biomarkers', regulatory/suppressive functions, migratory potential, etc.

Immune monitoring can also help determine the mechanism of action of an investigational drug, by revealing potential prognostic/predictive surrogate markers of clinical response, of immune related
adverse events (lrAEs) or of secondary resistance that can occur in clinical trial participants treated with Immune check point inhibitors, CART cells or therapeutic vaccines.

Active Biomarkers provides its partners with expert solutions through comprehensive design and adaptation of phenotypic and functional assays for characterization of immune cell subsets. Custom analytical methods are
optimized and qualified prior to routine sample testing and are guided by Active Biomarkers' decades of experience in cell culture, flow cytometry and ELISpot.
For more information on our immune monitoring services, please contact us at : info@active-biomarkers.com.
 

CLINICAL CHARACTERIZATION OF THE PD PROFILE OF A MONOCLONAL ANTIBODY

One of the major challenges encountered during the preclinical and clinical development of a new drug is the characterization of its pharmacokinetic (PK) and pharmacodynamie (PD) properties.
Preclinical PK/PD data issued from either in vitro or ex vivo animal studies, provide the basis for in silico modeling and simulation of the human PK/PD characteristics of the drug in
humans, leading to determination of the minimum anticipated biological effect level (MABEL) and the selection of the first human dose for clinical trials.
Clinical PK/PD data from early phase clinical trials are highly valued in that they confirm or update current PK and PD models in addition to optimizing dosing regimens for subsequent
efficacy and safety studies and later-stage clinical trials. Ligand binding assays are designed to quantify the binding of therapeutics to their targets, either by ELISA-based assays for
circulating targets or by receptor occupancy assays for those located on the cell surface. When combined with the PK profile, the resulting data can establish PK/PD relationships and trends,
which are essential for guiding dose decisions.

VALIDATION OF AN ULTRASENSITIVE IMMUNO-ASSAY FOR MONITORING NEURONAL DAMAGE

Our team has validated the SIMOA NF-Light Advantage Kit from Quanterix, evaluating its performance in terms of dynamic
range, precision, parallelism, selectivity, and stability in both blood and CSF samples. These methods have been used for
monitoring NfL in plasma and CSF from patients participating to a clinical study evaluating an innovative antibody-based therapy
for Alzheimer’s disease (AD).

Want to learn more? Read our case study!

Adsorption Assays for Biologics

Administration of antibody-based drug products by intravenous route requires dilution to low concentrations in i.v. solutions. At concentrations below 0.5 mg/mL, adsorption of biotherapeutics on plastic polymer injection devices such as i.v. bags, tubing and syringes may be substantial, leading to decrease by up to 40% at concentrations as low as 0.01 mg/mL when diluted in normal saline1.

So how to make sure that subjects consistently receive the desired dose?

Check our case study and don't hesitate to reach out to our expert team should you have any question.

ELISPOT - How to reduce assay variability

Most if not all vaccine candidates need robust methods to monitor their specific immunogenicity.

But clinical trial constraints as well as sample quality often make it challenging to achieve efficiently this objective.

Check our contribution to reducing ELISPOT assay variability.