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2017 ; 2
(8
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Cross-reactive dengue human monoclonal antibody prevents severe pathologies and
death from Zika virus infections
#MMPMID28422757
Kam YW
; Lee CY
; Teo TH
; Howland SW
; Amrun SN
; Lum FM
; See P
; Kng NQ
; Huber RG
; Xu MH
; Tan HL
; Choo A
; Maurer-Stroh S
; Ginhoux F
; Fink K
; Wang CI
; Ng LF
; Rénia L
JCI Insight
2017[Apr]; 2
(8
): ä PMID28422757
show ga
Zika virus (ZIKV) infections have been linked with neurological complications and
congenital Zika syndrome. Given the high level of homology between ZIKV and the
related flavivirus dengue virus (DENV), we investigated the level of
cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the
mAbs showed binding to ZIKV virions, with several exhibiting neutralizing
capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were
found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly
conserved fusion-loop peptide, a conformation-specific epitope on the E monomer,
and a quaternary epitope on the virion surface. The most potent ZIKV-neutralizing
mAb (SIgN-3C) was assessed in 2 type I interferon receptor-deficient (IFNAR-/-)
mouse models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C
rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant
with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce
antibody-dependent enhancement (ADE) in vitro but provided similar levels of
protection in vivo. In pregnant ZIKV-infected IFNAR-/- mice, treatment with
SIgN-3C or SIgN-3C-LALA significantly reduced viral load in the fetal organs and
placenta and abrogated virus-induced fetal growth retardation. Therefore,
SIgN-3C-LALA holds promise as a ZIKV prophylactic and therapeutic agent.
free
free
free
