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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Antimicrob+Agents+Chemother
2015 ; 59
(3
): 1558-68
Nephropedia Template TP
gab.com Text
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English Wikipedia
A high-affinity native human antibody neutralizes human cytomegalovirus infection
of diverse cell types
#MMPMID25534746
Kauvar LM
; Liu K
; Park M
; DeChene N
; Stephenson R
; Tenorio E
; Ellsworth SL
; Tabata T
; Petitt M
; Tsuge M
; Fang-Hoover J
; Adler SP
; Cui X
; McVoy MA
; Pereira L
Antimicrob Agents Chemother
2015[Mar]; 59
(3
): 1558-68
PMID25534746
show ga
Human cytomegalovirus (HCMV) is the most common infection causing poor outcomes
among transplant recipients. Maternal infection and transplacental transmission
are major causes of permanent birth defects. Although no active vaccines to
prevent HCMV infection have been approved, passive immunization with
HCMV-specific immunoglobulin has shown promise in the treatment of both
transplant and congenital indications. Antibodies targeting the viral
glycoprotein B (gB) surface protein are known to neutralize HCMV infectivity,
with high-affinity binding being a desirable trait, both to compete with
low-affinity antibodies that promote the transmission of virus across the
placenta and to displace nonneutralizing antibodies binding nearby epitopes.
Using a miniaturized screening technology to characterize secreted IgG from
single human B lymphocytes, 30 antibodies directed against gB were previously
cloned. The most potent clone, TRL345, is described here. Its measured affinity
was 1 pM for the highly conserved site I of the AD-2 epitope of gB.
Strain-independent neutralization was confirmed for 15 primary HCMV clinical
isolates. TRL345 prevented HCMV infection of placental fibroblasts, smooth muscle
cells, endothelial cells, and epithelial cells, and it inhibited postinfection
HCMV spread in epithelial cells. The potential utility for preventing congenital
transmission is supported by the blockage of HCMV infection of placental cell
types central to virus transmission to the fetus, including differentiating
cytotrophoblasts, trophoblast progenitor cells, and placental fibroblasts.
Further, TRL345 was effective at controlling an ex vivo infection of human
placental anchoring villi. TRL345 has been utilized on a commercial scale and is
a candidate for clinical evaluation.
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