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Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity
Injampa S. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity
ผู้แต่ง / หัวหน้าโครงการ (EN): Injampa S.
บทคัดย่อ (EN): . Dengue disease is a leading cause of illness and death in the tropics and subtropics. Most severe cases occur among patients secondarily infected with a different dengue virus (DENV) serotype compared with that from the first infection, resulting in antibody-dependent enhancement activity (ADE). Our previous study generated the neutralizing human monoclonal antibody, D23-1B3B9 (B3B9), targeting the first domain II of E protein, which showed strong neutralizing activity (NT) against all four DENV serotypes. However, at sub-neutralizing concentrations, it showed ADE activity in vitro. Methods. In this study, we constructed a new expression plasmid using the existing IgG heavy chain plasmid as a template for Fc modification at position N297Q bysite-directed mutagenesis. The resulting plasmid was then co-transfected with a light chain plasmid to produce full recombinant IgG (rIgG) in mammalian cells(N297Q-B3B9). This rIgG was characterized for neutralizing and enhancing activity by using different Fc R bearing cells. To produce sufficient quantities of B3B9 rIgG for further characterization, CHO-K1 cells stably secreting N297Q-B3B9 rIgG were then established. Results. The generated N297Q-B3B9 rIgG which targets the conserved N-terminal fusion loop ofDENVenvelope protein showed the same cross-neutralizing activity to all four DENV serotypes as those of wild type rIgG. In both FcγRI- and RII-bearing THP- 1 cells and FcγRII-bearing K562 cells, N297Q-B3B9 rIgG lacked ADE activity against all DENV serotypes at sub-neutralizing concentrations. Fortunately, the N297Q-B3B9rIgG secreted from stable cells showed the same patterns of NT and ADE activities as those of the N297Q-B3B9 rIgG obtained from transient expression against DENV2. Thus, the CHO-K1 stably expressing N297Q-B3B9 HuMAb can be developed as high producer stable cells and used to produce sufficient amounts of antibody for further characterization as a promising dengue therapeutic candidate. Discussion. Human monoclonal antibody, targeted to fusion loop of envelope domainII (EDII), was generated and showed cross-neutralizing activity to 4 serotypes of DENV, but did not cause any viral enhancement activity in vitro. This HuMAb could be further developed as therapeutic candidates. Subjects Biotechnology, Molecular Biology, Virology, Infectious Diseases. © 2017 Injampa et al.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033579945&doi=10.7717%2fpeerj.4021&partnerID=40&md5=2ab537deae2c9af2c7886faa1ac85b75
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): virus strain
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Injampa S.. "Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity". ไม่ระบุหน่วยงาน. ม.ป.ป.

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Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity
Injampa S.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Potent neutralizing human monoclonal antibodies preferentially target mature dengue virus particles: Implication for novel strategy for dengue vaccine Characterization of human CD8 T cell responses in dengue virus-infected patients from India Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand Sensitivity improvement of immunochromatographic strip test for infectious myonecrosis virus detection Production and characterization of a monoclonal antibody specific to 16 kDa antigen of Paramphistomum gracile B cell responses during secondary dengue virus infection are dominated by highly cross-reactive, memory-derived plasmablasts Adaptor protein 1A facilitates dengue virus replication Anti-Chikungunya Virus Monoclonal Antibody That Inhibits Viral Fusion and Release Broad-spectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development Antibody response to Zika and Dengue virus among the Zika realtime PCR positive cases in Thailand, 2016
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