Work packages > Work package 4

Start date or starting event: Month 1
Work package title: Development of vaccines and alternatives (antivirals) with rapid onset of immunity and based on safer production methods
Activity Type: RTD
Work Package Leader: IAH
Participants: CODA-VAR, IAH, LVRI, FUNPRECIT, AFSSA

Objectives

  • 1. Development and evaluation in mice and pigs of FMD vaccines that will be safe to produce using canine adenoviruses (Cav) expressing VP1 protein solely or associated with others capsid proteins
  • 2. Development and evaluation in mice and pigs of FMD vaccines that will be safe to produce using an attenuated encephalomyocarditis virus (EMCV) expressing the whole FMDV capsid
  • 3. Development of methods to reinforce and measure mucosal immunity against FMDV in cattle, thereby inducing early onset of protection and local blockage of the portal virus entry
  • 4. Design and construction of recombinant baculovirus (rBV) nucleopolyhedroviruses by inclusion of additional CpG motifs previously described as potential adjuvants for cattle
  • 5. Formulation of and evaluation of the immune responses and protective ability induced in mice and cattle by vaccines based on inactivated FMDV including the rBVs
    • Development and optimisation of potent and selective inhibitors of the replication of FMDV with potential for use as antiviral drugs

Description of work

  • Task 1. Production and evaluation of Cav-FMDV vaccines
    •     1.1. Evaluation of cross-reactive immunity against Cav vector in cattle and pigs
    •     1.2. Evaluation of Cav vector induced immune response in pigs
    •     1.3. Production of Cav-FMDV vaccine
    •     1.4. Evaluation of Cav-FMDV vaccines
  • Task 2. Production and evaluation of EMCV-FMD vaccines
    •     2.1. Production of the recombinant virus
    •     2.2. Evaluation of the EMCV-FMD vaccine virulence and efficacy in mice and pigs
  • Task 3. Development of methods to reinforce and measure mucosal immunity against FMDV in cattle
    •     3.1 Use of mucosal vectors to stimulate local immunity
    •     3.2 Mucosal delivery systems and adjuvants
    •     3.3 Measurement of mucosal immunity
  • Task 4. Assessment of recombinant BV as adjuvants for FMDV vaccines
  • Task 5. Development and optimisation of potent and selective inhibitors of FMDV replication
    •     5.1. In vitro identification of new inhibitors
    •     5.2. In vitro characteristics of the antiviral activity and molecular target identification
    •     5.3. In vivo activity

Deliverables

  • 4.1. rBVs carrying CpG sequences specific for bovines (M8)
  • 4.2. Identified and optimised in vitro promising anti-FMDV antiviral compounds (M12)
  • 4.3. Identified molecular target for antiviral activity (M18)
  • 4.4. Recombinant Cav-FMD and EMC-FMD viruses (M20)
  • 4.5. Report on the knowledge on in vivo activity, toxicology and pharmacokinetics in guinea pigs (M24)
  • 4.6. Report on the immune response in mice and pigs vaccinated with Cav-FMD and EMC-FMDV vaccines (M30)
  • 4.7. Report on the immunomodulation and protection induced by the rBVs in the FMDV model in mice (M30)
  • 4.8. Report on the efficacy of Cav-FMD and EMC-FMDV vaccines (M36)
  • 4.9. Report on efficacy of different systems for mucosal delivery of conventional vaccine antigen (M36)
  • 4.10. Report on efficacy of mucosally delivered SeV vectors expressing type 1 bovine interferons (M36)
  • 4.11. Report on efficacy of mucosally delivered AdV vectors expressing FMDV capsids (M36)
  • 4.12. Report on the knowledge on in vivo antiviral activity, toxicology (including residue-analysis), pharmacokinetics, drug-resistance and reduction of transmission of the selected antiviral compounds in cattle or pigs (proof-of-concept) (M36)
  • 4.13. Report on the immune response induced by experimental BV vaccines in cattle (M36)
  • 4.14. Samples for diagnostic test development/optimisation (M36)
  • 4.15. Peer-reviewed publications (M36)

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