tailieunhanh - Báo cáo y học: "A stabilized HIV-1 envelope glycoprotein trimer fused to CD40 ligand targets and activates dendritic cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: A stabilized HIV-1 envelope glycoprotein trimer fused to CD40 ligand targets and activates dendritic cells. | Melchers et al. Retrovirology 2011 8 48 http content 8 1 48 RETR0VIR0L0GY RESEARCH Open Access A stabilized HIV-1 envelope glycoprotein trimer fused to CD40 ligand targets and activates dendritic cells 1 2 11 11 Mark Melchers Katie Matthews Robert P de Vries Dirk Eggink Thijs van Montfort Ilja Bontjer 1 2 1 2 1 2 Carolien van de Sandt Kathryn David Ben Berkhout John P Moore and Rogier W Sanders Abstract Background One reason why subunit protein and DNA vaccines are often less immunogenic than live-attenuated and whole-inactivated virus vaccines is that they lack the co-stimulatory signals provided by various components of the more complex vaccines. The HIV-1 envelope glycoprotein complex Env is no exception to this rule. Other factors that limit the induction of neutralizing antibodies against HIV-1 lie in the structure and instability of Env. We have previously stabilized soluble trimeric mimics of Env by introducing a disulfide bond between gp120 and gp41 and adding a trimer stabilizing mutation in gp41 gp140 . Results We further stabilized the gp140 using a GCN4-based isoleucine zipper motif creating gp140. In order to target to immune cells including dendritic cells while at the same time activating these cells we fused to the active domain of CD40 ligand CD40L which may serve as a cis-adjuvant . The Env component of the fusion construct bound to CD4 and neutralizing antibodies while the CD40L moiety interacted with CD40. Furthermore the chimeric molecule was able to signal efficiently through CD40 and induce maturation of human dendritic cells. Dendritic cells secreted IL-6 IL-10 and IL-12 in response to stimulation by and were able to activate naive T cells. Conclusions Chimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells. Targeting and activating immune cells using CD40L and other cis-adjuvants may improve subunit protein .