Tkachuk A P, Gushchin V A, Potapov V D, Demidenko A V, Lunin V G, Gintsburg A L
Translational Biomedicine Laboratory, N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Moscow, Russia.
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
PLoS One. 2017 Apr 28;12(4):e0176784. doi: 10.1371/journal.pone.0176784. eCollection 2017.
New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models. Results show that in both infectious models, GamTBvac has a strong immunogenicity and significant protective effect against Mycobacterium tuberculosis strain H37Rv under aerosol and intravenous challenges. GamTBvac showed a particularly strong protective effect as a BCG booster vaccine.
对抗结核病造成的全球威胁急需新型创新疫苗。高效的成分——抗原和佐剂——对于现代重组结核病疫苗的研发至关重要。本研究描述了一种新疫苗（GamTBvac），它由两种分枝杆菌抗原融合体（Ag85A和ESAT6-CFP10）组成，其中葡聚糖结合结构域固定在葡聚糖上，并与由DEAE-葡聚糖核心和CpG寡脱氧核苷酸（TLR9激动剂）组成的佐剂混合。在小鼠和豚鼠结核病模型中，对GamTBvac及其成分进行了GamTBvac初免/加强免疫和卡介苗初免/GamTBvac加强免疫的免疫原性和保护效力评估。结果表明，在两种感染模型中，GamTBvac在气溶胶和静脉注射攻击下对结核分枝杆菌H37Rv菌株具有很强的免疫原性和显著的保护作用。作为卡介苗加强疫苗，GamTBvac显示出特别强的保护作用。
