Human monoclonal antibodies to neutralize all dengue virus serotypes using lymphocytes from patients at acute phase of the secondary infection.
The global spread of the four dengue virus serotypes (DENV-1 to -4) has made this virus a major and growing public health concern. Generally, pre-existing neutralizing antibodies derived from primary infection play a significant role in protecting against subsequent infection with the same serotype. By contrast, these pre-existing antibodies are believed to mediate a non-protective response to subsequent heterotypic DENV infections, leading to the onset of dengue illness. In this study, we prepared hybridomas producing human monoclonal antibodies (HuMAbs) against DENV using peripheral blood mononuclear cells (PBMCs) from patients in the acute phase (around 1 week after the onset of illness) or the convalescent phase (around 2weeks after the onset of illness) of secondary infection. Interestingly, a larger number of hybridoma clones was obtained from patients in the acute phase than from those in the convalescent phase. Most HuMAbs from acute-phase infections were cross-reactive with all four DENV serotypes and showed significant neutralization activity to all four DENV serotypes. Thus, secondary DENV infection plays a significant role in stimulating memory cells to transiently increase the number of antibody-secreting plasma cells in patients in the early phase after the secondary infection. These HuMAbs will enable us to better understand the protective and pathogenic effects of DENV infection, which could vary greatly among secondarily-infected individuals.
Center of Excellence for Antibody Research, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand.
Chayanee
C
Setthapramote
Tadahiro
T
Sasaki
Orapim
O
Puiprom
Kriengsak
K
Limkittikul
Pannamthip
P
Pitaksajjakul
Chonlatip
C
Pipattanaboon
Mikiko
M
Sasayama
Pornsawan
P
Leuangwutiwong
Weerapong
W
Phumratanaprapin
Supat
S
Chamnachanan
Teera
T
Kusolsuk
Akanitt
A
Jittmittraphap
Azusa
A
Asai
Juan Fernando
JF
Arias
Itaru
I
Hirai
Motoki
M
Kuhara
Yoshinobu
Y
Okuno
Takeshi
T
Kurosu
Pongrama
P
Ramasoota
Kazuyoshi
K
Ikuta
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000276:immunology; D002522:Chlorocebus aethiops; D060085:Coinfection; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D012703:Serotyping; D014709:Vero Cells; D014764:Viral Proteins / Q000276:immunology*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D014764:Viral Proteins