Etude du rôle des mastocytes dans l’immunité mucosale anti-trichinella : activation in vitro des mastocytes de petits rongeurs par les antigènes de Trichinella spiralis

Diplôme : Dr. d'Universit

Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV

International audienceAs an alternative strategy to classical inactivated viral vaccine against FMDV, naked DNA vaccine is attractive because of safety, flexibility and low cost. However DNA vaccination is usually poorly efficient in target species. Indeed we found that naked DNA plasmids encoding for P1-2A3C3D and GM-CSF proteins did not induce any detectable immunity against FMDV in sheep. Interestingly, we demonstrate herein that formulations of DNA on poly(d,l-lactide-co-glycolide) (PLG) or in lipofectin triggered divergent types of immune responses: PLG stimulated a T cell response and could elicit significant neutralising antibody titers, whereas lipofectin generated even higher antibody titers but no significant T cell response. The DNA/PLG regimen used in five sheep protected against clinical symptoms and viraemia and prevented the carrier state in four of them. Thus formulated DNA can be remarkably efficient against FMDV in a ruminant species that is usually refractory to DNA vaccination

Co-expression of the Bcl-xL antiapoptotic protein enhances the induction of Th1-like immune responses in mice immunized with DNA vaccines encoding FMDV B and T cell epitopes

WOS: 000323269300001PubMed ID: 23483312Foot-and-mouth disease (FMD) is one of the most devastating animal diseases, affecting all cloven-hoofed domestic and wild animal species. Previous studies from our group using DNA vaccines encoding FMD virus (FMDV) B and T cell epitopes targeted to antigen presenting cells, allowed demonstrating total protection from FMDV homologous challenge in those animals efficiently primed for both humoral and cellular specific responses (Borrego et al. Antivir Res 92:359-363, 2011). In this study, a new DNA vaccine prototype expected to induce stronger and cross-reactive immune responses against FMDV which was designed by making two main modifications: i) adding a new B-cell epitope from the O-serotype to the B and T-cell epitopes from the C-serotype and ii) using a dual promoter plasmid that allowed inserting a new cistron encoding the anti-apoptotic Bcl-xL gene under the control of the internal ribosomal entry site (IRES) of encephalomyocarditis virus aiming to increase and optimize the antigen presentation of the encoded FMDV epitopes after in vivo immunization. In vitro studies showed that Bcl-xL significantly prolonged the survival of DNA transfected cells (p < 0.001). Accordingly, vaccination of Swiss out-bred mice with the dual promoter plasmid increased the total IgG responses induced against each of the FMDV epitopes however no significant differences observed between groups. The humoral immune response was polarized through IgG2a in all vaccination groups (p < 0.05); except peptide T-3A; in correspondence with the Th1-like response observed, a clear bias towards the induction of specific IFN-gamma secreting CD4(+) and CD8(+) T cell responses was also observed, being significantly higher (p < 0.05) in the group of mice immunized with the plasmid co-expressing Bcl-xL and the FMDV B and T cell epitopes.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [110O809]; Ege UniversityEge University; Science and Technology CenterScience and Technology Development Fund (STDF) [2011BIL020]; [PCI2005-A7-0092]This project is partly funded by The Scientific and Technological Research Council of Turkey (110O809), Ege University, Science and Technology Center (2011BIL020) and a complementary action between Spain and Turkey (PCI2005-A7-0092). The authors acknowledge EP Martin, Ph.D. and JM Marques, Ph.D. for their technical help. The specific MAbs against FMDV were kindly provided by Emilliana Brocchi, Ph.D., from Istituto Zooprofilattico Sperimentale Della Lombardia, Italy