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Title: Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection
Authors: Tadahiro Sasaki
Chayanee Setthapramote
Takeshi Kurosu
Mitsuhiro Nishimura
Azusa Asai
Magot D. Omokoko
Chonlatip Pipattanaboon
Pannamthip Pitaksajjakul
Kriengsak Limkittikul
Arunee Subchareon
Panjaporn Chaichana
Tamaki Okabayashi
Itaru Hirai
Pornsawan Leaungwutiwong
Ryo Misaki
Kazuhito Fujiyama
Ken ichiro Ono
Yoshinobu Okuno
Pongrama Ramasoota
Kazuyoshi Ikuta
Osaka University
Mahidol University
Medical & Biological Laboratories Co, Ltd
Keywords: Immunology and Microbiology;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jun-2013
Citation: Antiviral Research. Vol.98, No.3 (2013), 423-431
Abstract: Public health concern about dengue diseases, caused by mosquito-borne infections with four serotypes of dengue virus (DENV-1-DENV-4), is escalating in tropical and subtropical countries. Most of the severe dengue cases occur in patients experiencing a secondary infection with a serotype that is different from the first infection. This is believed to be due to antibody-dependent enhancement (ADE), by which one DENV serotype uses pre-existing anti-DENV antibodies elicited in the primary infection to facilitate entry of a different DENV serotype into the Fc receptor-positive macrophages. Recently, we prepared a number of hybridomas producing human monoclonal antibodies (HuMAbs) by using peripheral blood lymphocytes from Thai patients at acute phase of secondary infection with DENV-2. Here, we characterized 17 HuMAbs prepared from two patients with dengue fever (DF) and one patient with dengue hemorrhagic fever (DHF) that were selected as antibodies recognizing viral envelope protein and showing higher neutralization activity to all serotypes. In vivo evaluation using suckling mice revealed near perfect activity to prevent mouse lethality following intracerebral DENV-2 inoculation. In a THP-1 cell assay, these HuMAbs showed ADE activities against DENV-2 at similar levels between HuMAbs derived from DF and DHF patients. However, the F(ab')2fragment of the HuMAb showed a similar virus neutralization activity as original, with no ADE activity. Thus, these HuMAbs could be one of the therapeutic candidates against DENV infection. © 2013 Elsevier B.V.
ISSN: 18729096
Appears in Collections:Scopus 2011-2015

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