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Potent neutralizing human monoclonal antibodies preferentially target mature dengue virus particles: Implication for novel strategy for dengue vaccine
Tsai W.-Y. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Potent neutralizing human monoclonal antibodies preferentially target mature dengue virus particles: Implication for novel strategy for dengue vaccine
ผู้แต่ง / หัวหน้าโครงการ (EN): Tsai W.-Y.
บทคัดย่อ (EN): The four serotypes of dengue virus (DENV) cause the most important mosquito-borne viral disease in humans. The envelope (E) protein is the major target of neutralizing antibodies and contains 3 domains (domain I [DI], DII, and DIII). Recent studies reported that human monoclonal antibodies (MAbs) recognizing DIII, the D1/DII hinge, the E-dimer epitope, or a quaternary epitope involving DI/DII/DIII are more potently neutralizing than those recognizing the fusion loop (FL) of DII. Due to inefficient cleavage of the premembrane protein, DENV suspensions consist of a mixture of mature, immature, and partially immature particles. We investigated the neutralization and binding of 22 human MAbs to DENV serotype 1 (DENV1) virions with differential maturation status. Compared with FL MAbs, DIII, DI/DII hinge, and E-dimer epitope MAbs showed higher maximum binding and avidity to mature particles relative to immature particles; this feature may contribute to the strong neutralizing potency of such MAbs. FL-specific MAbs required 57 to 87% occupancy on mature particles to achieve half-maximal neutralization (NT 50 ), whereas the potently neutralizing MAbs achieved NT 50 states at 20 to 38% occupancy. Analysis of the MAb repertoire and polyclonal sera from patients with primary DENV1 infection supports the immunodominance of cross-reactive anti-E antibodies over type-specific antibodies. After depletion with viral particles from a heterologous DENV serotype, the type-specific neutralizing antibodies remained and showed binding features shared by potent neutralizing MAbs. Taken together, these findings suggest that the use of homogeneous mature DENV particles as an immunogen may induce more potent neutralizing antibodies against DENV than the use of immature or mixed particles. Copyright © 2018 American Society for Microbiology. All Rights Reserved.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056312854&doi=10.1128%2fJVI.00556-18&partnerID=40&md5=e9824902fd3958a1943c184681ba0248
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): virus particle
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Potent neutralizing human monoclonal antibodies preferentially target mature dengue virus particles: Implication for novel strategy for dengue vaccine
Tsai W.-Y.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity 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 Periods of high dengue transmission defined by rainfall do not impact efficacy of dengue vaccine in regions of endemic disease Adaptor protein 1A facilitates dengue virus replication Actin interacts with dengue virus 2 and 4 envelope proteins Microparticles provide a novel biomarker to predict severe clinical outcomes of dengue virus infection Relationships between dengue virus infection in mosquito vector, (Aedes aegypti), dengue cases and weather conditions in Samut Sakhon Province, Thailand Dengue forecasting model using sarima model to predict the incidence of dengue in Thailand Divergence of the dengue virus type 2 Cosmopolitan genotype associated with two predominant serotype shifts between 1 and 2 in Surabaya, Indonesia, 2008-2014
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