tailieunhanh - Báo cáo y học: "Role of innate signalling pathways in the immunogenicity of alphaviral replicon-based vaccines"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Role of innate signalling pathways in the immunogenicity of alphaviral replicon-based vaccines | Năslund et al. Virology Journal 2011 8 36 http content 8 1 36 J VIROLOGY JOURNAL RESEARCH Open Access Role of innate signalling pathways in the immunogenicity of alphaviral replicon-based vaccines Tanja I Naslund1 Linda Kostic2 Eva KL Nordstrom2 3 Margaret Chen2 4 Peter Liljestrom1 2 Abstract Background Alphaviral replicon-based vectors induce potent immune responses both when given as viral particles VREP or as DNA DREP . It has been suggested that the strong immune stimulatory effect induced by these types of vectors is mediated by induction of danger signals and activation of innate signalling pathways due to the replicase activity. To investigate the innate signalling pathways involved mice deficient in either toll-like receptors or downstream innate signalling molecules were immunized with DREP or VREP. Results We show that the induction of a CD8 T cell response did not require functional TLR3 or MyD88 signalling. However IRF3 converging several innate signalling pathways and important for generation of pro-inflammatory cytokines and type I IFNs was needed for obtaining a robust primary immune response. Interestingly type I interferon IFN induced by most innate signalling pathways had a suppressing effect on both the primary and memory T cell responses after DREP and VREP immunization. Conclusions We show that alphaviral replicon-based vectors activate multiple innate signalling pathways which both activate and restrict the induced immune response. These results further show that there is a delicate balance in the strength of innate signalling and induction of adaptive immune responses that should be taken into consideration when innate signalling molecules such as type I IFNs are used as vaccine adjuvant. Introduction Alphaviral replicon-based vectors are attractive vaccine candidates since they induce strong immune responses in various animal models. The alphaviral replicon encodes an alphavirus replicase an RNA polymerase which strongly .