Download 56. Novel immunological approaches for emergency FMD vaccines

Appendix 56
Novel immunological approaches for emergency FMD vaccines inducing mucosal immunity
Artur Summerfield, Laurence Guzylack-Piriou, Leslie Saurer and Kenneth C McCullough
Institute of Virology and Immunoprophylaxis, 3147 Mittelhaeusern, Switzerland
Introduction
Vaccination has the potential to reduce large-scaling culling to control future FMD outbreaks in
Europe. Due to the rapidity of FMDV replication and spread, the development of vaccine formulations
inducing early protection is critical for an emergency scenario. Our strategy is to stimulate innate
antiviral immune defence by targeting natural interferon producing cells (NIPC). One possibility are
CpG oligonucleotides (ODN), shown to induce non-specific protection in murine models. This requires
the identification and characterization of CpG motifs targeting NIPC representing the main source of
interferon-α (IFN-α) production in the immune system. Induction of mucosal immunity is another
critical element to improve current vaccines. Neutralization of FMDV at mucosal surfaces by
antibodies could prevent virus entry and establishment of the carrier status. Consequently, a second
goal of our investigations is to induce mucosal immunity following parenteral vaccination. To this end,
the immunological barrier separating the systemic from mucosal immunological compartments has to
be overcome.
Materials and Methods
Porcine plasmacytoid DC were enriched from peripheral blood and stimulated with various CpG ODN.
INF-α in culture supernatants was detected by ELISA. Pigs were vaccinated with FMDV vaccine
adjuvanted with CpG ODN, and the antiviral response monitored using INF-α and Mx protein
detection. Modulation of chemokine receptor expression and DC migration was analysed by flow
cytometry and chemotaxis assays.
Results and discussion
CpG type A capable of inducing strong INF-α responses by stimulating plasmacytoid DC were
identified and characterized. Their in vivo effect on the innate immune system is under current
investigation to determine optimum doses and formulations, and to test in challenge experiments.
Current concepts forming a basis for mucosal immunity induction will be presented, based on
modulation of DC and lymphocyte migration. In vitro culture systems enabling a systematic and
controlled approach to the question are currently and will be discussed.
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