title: Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection.
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')2 fragment 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.
authors.affiliation: Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Sasaki
authors.forename: Chayanee
authors.initials: C
authors.lastname: Setthapramote
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nishimura
authors.forename: Azusa
authors.initials: A
authors.lastname: Asai
authors.forename: Magot D
authors.initials: MD
authors.lastname: Omokoko
authors.forename: Chonlatip
authors.initials: C
authors.lastname: Pipattanaboon
authors.forename: Pannamthip
authors.initials: P
authors.lastname: Pitaksajjakul
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Limkittikul
authors.forename: Arunee
authors.initials: A
authors.lastname: Subchareon
authors.forename: Panjaporn
authors.initials: P
authors.lastname: Chaichana
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Itaru
authors.initials: I
authors.lastname: Hirai
authors.forename: Pornsawan
authors.initials: P
authors.lastname: Leaungwutiwong
authors.forename: Ryo
authors.initials: R
authors.lastname: Misaki
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Fujiyama
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Ono
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Okuno
authors.forename: Pongrama
authors.initials: P
authors.lastname: Ramasoota
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D060085:Coinfection / Q000276:immunology / Q000821:virology; D003715:Dengue / Q000276:immunology / Q000628:therapy*; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012720:Severity of Illness Index; D014759:Viral Envelope Proteins / Q000276:immunology; D053586:Virus Internalization; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins