Work packages > Work package 2

Start date or starting event: Month 1
Work package title: Reduction and refinement of in vivo vaccine quality tests by in vitro methods
Activity Type: RTD
Work Package Leader: CODA-VAR
Participants: CODA-VAR, IAH, CVI, IZSLER, FLI, FUNPRECIT, IVI, UGLA, Merial

Objectives
In light of the 3R (Refinement, Reduction, Replacement) concept on animal use for regulatory testing, this work package aims at:

  • 1. Determining and validating the correlation between in vitro laboratory tests (serology, measurement of IFN-γ release, capacity of sera to promote FcR-mediated FMDV phagocytosis, capacity of sera to promote FcR-mediated IFN-α responses in pDC) and in vivo protection based on experimental and field sera
  • 2. Harmonising tests used by different partners to assess vaccine efficacy
  • 3. Developing in vitro immunoassays to monitor the NSP content and reduction during the vaccine purification process
  • 4. Developing alternative methods for 146S (140S) quantification
Consequently, future FMD vaccine quality tests could rely on in vitro alternatives while maintaining a high level of confidence in the overall quality of FMD vaccine batches.

Description of work

  • Task 1. Refinement of in vivo vaccine potency tests by in vitro alternatives
    •     1.1 Refinement of in vivo vaccine potency tests by a serological approach
    •     1.2 Refinement of in vivo vaccine potency tests by alternative methods based on cell-mediated IFN-γ immune responses (partners 1, 2, 12 and 14)
    •     1.3 Refinement of in vivo vaccine potency tests by other in vitro cell-mediated correlates of protection (partner 10)
  • Task 2. Replacement of in vivo vaccine purity tests by in vitro alternatives
    •     2.1. Development of a MAb-inhibition ELISA to quantify the NSP content in vaccines
    •     2.2. Development of highly sensitive immunoblotting and ELISA methods for detection of NSP in vaccine antigens
  • Task 3. Developing alternative methods for 146S (140S) quantification in viral products and vaccines
  • Task 4. Validation of the use of serology to estimate the protection level in vaccinated populations

Deliverables

  • 2.1 A database of sera from vaccine potency tests (M3)
  • 2.2 A database of re-stimulated plasma samples suitable for IFN-γ measurement (M3)
  • 2.3 Consortium-accepted “reference” sera for assessing the correlation between serology post-vaccination and protection against challenge (M6)
  • 2.4 Development of statistical models correlating serology post-vaccination to protection against challenge (M12)
  • 2.5 Improved automated method for the quantification of 140S particles by means of sucrose gradients (M16)
  • 2.6 Report of the workshop on harmonising serological results/methods and protection against challenge, including data on VNT and ELISA correlations in and between partners (M18)
  • 2.7 Application of FcR-dependent FMDV phagocytosis assays as potential correlate of protection (M18)
  • 2.8 Statistical models correlating IFN-γ responses post-vaccination to protection against challenge (M24)
  • 2.9 Application of FcR-dependent IFN-α responses as potential correlates of protection (M24)
  • 2.10 Standardised protocol for 140S quantification in vaccines by liquid chromatography (M24)
  • 2.11 In vitro immunoassays to quantify vaccine purity by the absence of NSP (M30)
  • 2.12 Standardised procedure to assess FMD vaccine potency by serology (M36)
  • 2.13 Standardised procedure to assess FMD vaccine potency by IFN-γ measurement (M36)
  • 2.14 Statistical models combining serological and IFN-γ responses and correlating them to a probability of protection (M36)
  • 2.15 Comparison of between serological test correlation in experimental and field vaccinates (M36)
  • 2.16 Guidelines to interpret results of post-vaccination sero-surveillance with reference to protection (M36)
  • 2.17 Application of FcR-expressing reporter cell lines to measure antibody-based correlates of protection (M36)
  • 2.18 MAb-based ELISAs for the quantification of 146S (140S) and 12S particles in viral products and vaccines, including reference to vaccine potency (M36)
  • 2.19 Peer-reviewed publications (M36)

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