Oral Presentation International Veterinary Immunology Symposium 2016

Development of a TLR-ligand adjuvanted liposome-based vaccine to enhance the duration of immunity using systems immunology (#80)

Roman Othmar Braun 1 2 , Livia Brunner 3 , Kurt Wyler 4 , Gaël Auray 2 , Arnaud Baumann 2 , Obdulio García-Nicolás 2 , Sylvie Python 2 , Beatrice Zumkehr 2 , Nicolas Collin 3 , Irene Keller 4 , Véronique Gaschen 5 , Michael Stoffel 5 , Rémy Bruggmann 4 , Christophe Barnier-Quer 3 , Artur Summerfield 2
  1. Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
  2. Institute of Virology and Immunology, Mittelhäusern, Switzerland
  3. Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Lausanne, Switzerland
  4. Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland
  5. Division of Veterinary Anatomy, University of Bern, Bern, Switzerland

Newly emerging and existing infectious diseases pose an ongoing threat to humans and livestock. For some devastating infectious diseases, vaccines are lacking or provide insufficient levels of protection. One key aim for novel vaccines is the induction of long-term protective immunity. Based on the concept that a strong trigger is needed at time of vaccination, we are developing a liposome-based vaccine platform that allows flexibility in terms of antigen incorporation for optimal antigen delivery as well as a strong activation of innate immunity. To this end, using the pig model, we are specifically targeting Toll-like receptors (TLR) on dendritic cells (DC) and B cells, which are then analyzed in terms of cytokines and co-stimulatory molecule expression, proliferation and immunoglobulin secretion. Furthermore, we are investigating the DC-subset-dependent responses. Stimulation with ligands for TLR 4, TLR7/8 and TLR9 were most promising for further studies. In the model of foot-and-mouth disease virus, we are currently testing such formulations containing one TLR ligand or combinations of ligands for their ability to induce long-lasting neutralizing antibodies levels in sheep. Our results confirm the validity of the concept established in murine models but also indicate some species differences with respect to the responses induced by TLR ligands. Furthermore, using systems immunological approaches we are analyzing the transcriptomic expression using RNA-sequencing after immunization and compare our findings to similar studies in humans to identify markers of protection.