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2017 ; 7
(ä): 157
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Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent
Enhancement of Dengue Virus Infection
#MMPMID28536674
Wang M
; Yang F
; Huang D
; Huang Y
; Zhang X
; Wang C
; Zhang S
; Zhang R
Front Cell Infect Microbiol
2017[]; 7
(ä): 157
PMID28536674
show ga
Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection
only leads to self-limited dengue fever. But secondary infection with another
serotype carries a higher risk of increased disease severity, causing
life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS).
Serotype cross-reactive antibodies facilitate DENV infection in
Fc-receptor-bearing cells by promoting virus entry via Fc? receptors (Fc?R), a
process known as antibody dependent enhancement (ADE). Most studies suggested
that enhancing antibodies were mainly specific to the structural premembrane
protein (prM) of DENV. However, there is still no effective drugs or vaccines to
prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human
sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could
significantly enhance DENV-1 infection in K562 cells. Then we developed
anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c
mice. Results showed that these polyclonal antibodies can dramatically reduce ADE
phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE
effect of prM-AIDs in vivo, interferon-? and ? receptor-deficient mice (AG6) were
used as the mouse model for DENV infection. We found that administration of
DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10
(IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar
to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged
AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative
control level. Of note, the number of platelets in peripheral blood of prM-AIDs
group were significantly increased at day 3 post infection with DENV-1 compared
that of prM-mAb group. These results confirmed that our prM-AIDs could prevent
ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies
might be a new choice to be considered to treat DENV infection.