Nanodelivery system enhances the immunogenicity of dengue-2 nonstructural protein 1, DENV-2 NS1
VACCINE
Authors: Jearanaiwitayakul, Tuksin; Sunintaboon, Panya; Chawengkittikul, Runglawan; Limthongkul, Jitra; Midoeng, Panuwat; Warit, Saradee; Ubol, Sukathida
Abstract
Nonstructural protein 1 (NS1) of dengue virus (DENV) is currently recognized as a dengue vaccine candidate. Unfortunately, most of non-replicating immunogens typically stimulate unsatisfactory immune responses, thus, the additional adjuvant is required. In this study, C-terminal truncated DENV-2 NS1 loaded in N,N,N, trimethyl chitosan nanoparticles (NS1(1-279) TMC NPs) was prepared through the ionic gelation method. The immunogenicity of NS1(1-279) TMC NPs was investigated using human ex vivo as well as the murine model. Through a human ex vivo model, it was demonstrated in this study that not only can TMC particles effectively deliver NS1(1-279) protein into monocyte-derived dendritic cells (MoDCs), but also potently stimulate those cells, resulting in increased expression of maturation marker (CD83), costimulating molecules (CD80, CD86 and HLA-DR) and markedly secreted various types of innate immune cytokines/chemokines. Moreover, mice administered with NS1(1-279) TMC NPs strongly elicited both antibody and T cell responses, produced higher levels of IgG, IgG1, IgG2a and potently activated CD8(+) T cells, as compared to mice administered with soluble NS1(1-279). Importantly, we further demonstrated that anti-NS1(1-279) antibody induced by this platform of NS1(1-279) effectively eliminated DENV-2 infected cells through antibody dependent complement-mediated cytotoxicity. Significantly, anti-DENV2 NS1(1-279) antibody exerted cross-antiviral activity against DENV-1 and -4 but not against DENV-3 infected cells. These findings demonstrate that TMC exerts a desirable adjuvant for enhancing delivery and antigenicity of NS1 based dengue vaccine. (C) 2020 Elsevier Ltd. All rights reserved.
Establishment and characterization of a novel 'double-hit' follicular lymphoma cell line, FL-SJC
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Authors: Chen, Min; Jiang, Guoxiong; Liu, Yichen; Li, Dongya; Li, Tiantian; Peng, Jie; Jiang, Qian; You, Haiyan; Ba, Rong; Pan, Jinlan; Li, Mei; Long, Weiguo; Yan, Jinsong; Zhu, Yan; Wang, Yun; Xi, Xiaodong; Mao, Jianhua; Shi, Xiaofeng
Abstract
About 5 per cent of follicular lymphoma (FL) cases are double-hit (DH) lymphomas. Double-hit follicular lymphoma (DHFL) cell lines can improve our understanding and drug development on FL. But there are only few DHFL cell lines. Here, we established a new MYC/BCL2 DHFL cell line, FL-SJC. The cells were obtained from the hydrothorax of a patient with MYC/BCL2 DHFL and cultured for 140 passages in vitro. FL-SJC cells demonstrated CD19(++), CD20(+), CD22(++), HLA-DR+, CD10(+), CD38(+), Lambda(+) CD23(-), CD5(-) and Kappa(-). The chromosome karyotypic analysis confirmed the co-existence of t(8;22)(q24;q11) and t(14;18)(q32;q21), as well as additional abnormalities involving chromosomes 2 and 3. Fluorescence in situ hybridization analysis (FISH) showed IGH/BCL2 fusion gene and the MYC rearrangement. In addition, the FL-SJC cells displayed KMT2D/MLL2 and CREBBP gene mutations. After subcutaneous inoculation of FL-SJC cells, the SCID mice developed solid tumour masses within 6-8 weeks. FL-SJC cells were proven to be free of Epstein-Barr (EB) virus infection and be multidrug-resistant. In a conclusion, the FL-SJC cell line has been identified as a novel MYC/BCL2 double-hit follicular lymphoma that can be used as a potentially available tool for the clinical and basic research, together with the drug development for MYC/BCL2 DHFL.