Research output: Contribution to journal › Article › peer-review
Post-exposure administration of chimeric antibody protects mice against European, Siberian, and Far-Eastern subtypes of tickborne encephalitis virus. / Matveev, Andrey L.; Kozlova, Irina V.; Stronin, Oleg V. et al.
In: PLoS ONE, Vol. 14, No. 4, 0215075, 08.04.2019.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Post-exposure administration of chimeric antibody protects mice against European, Siberian, and Far-Eastern subtypes of tickborne encephalitis virus
AU - Matveev, Andrey L.
AU - Kozlova, Irina V.
AU - Stronin, Oleg V.
AU - Khlusevich, Yana A.
AU - Doroshchenko, Elena K.
AU - Baykov, Ivan K.
AU - Lisak, Oksana V.
AU - Emelyanova, Ljudmila A.
AU - Suntsova, Olga V.
AU - Matveeva, Vera A.
AU - Savinova, Julia S.
AU - Tikunova, Nina V.
PY - 2019/4/8
Y1 - 2019/4/8
N2 - Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen. It belongs to the Flaviviridae family and causes severe human neuroinfections. In this study, protective efficacy of the chimeric antibody chFVN145 was examined in mice infected with strains belonging to the Far-Eastern, European, and Siberian subtypes of TBEV, and the antibody showed clear therapeutic efficacy when it was administered once one, two, or three days after infection. The efficacy was independent of the TBEV strain used to infect the mice; however, the survival rate of the mice was dependent on the dose of TBEV and of the antibody. No enhancement of TBEV infection was observed when the mice were treated with non-protective doses of chFVN145. Using a panel of recombinant fragments of the TBEV glycoprotein E, the neutralizing epitope for chFVN145 was localized in domain III of the TBEV glycoprotein E, in a region between amino acid residues 301 and 359. In addition, three potential sites responsible for binding with chFVN145 were determined using peptide phage display libraries, and 3D modeling demonstrated that the sites do not contact the fusion loop and, hence, their binding with chFVN145 does not result in increased attachment of TBEV to target cells.
AB - Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen. It belongs to the Flaviviridae family and causes severe human neuroinfections. In this study, protective efficacy of the chimeric antibody chFVN145 was examined in mice infected with strains belonging to the Far-Eastern, European, and Siberian subtypes of TBEV, and the antibody showed clear therapeutic efficacy when it was administered once one, two, or three days after infection. The efficacy was independent of the TBEV strain used to infect the mice; however, the survival rate of the mice was dependent on the dose of TBEV and of the antibody. No enhancement of TBEV infection was observed when the mice were treated with non-protective doses of chFVN145. Using a panel of recombinant fragments of the TBEV glycoprotein E, the neutralizing epitope for chFVN145 was localized in domain III of the TBEV glycoprotein E, in a region between amino acid residues 301 and 359. In addition, three potential sites responsible for binding with chFVN145 were determined using peptide phage display libraries, and 3D modeling demonstrated that the sites do not contact the fusion loop and, hence, their binding with chFVN145 does not result in increased attachment of TBEV to target cells.
KW - ENHANCEMENT
KW - ENVELOPE GLYCOPROTEIN
KW - EPIDEMIOLOGY
KW - IMMUNOGLOBULIN
KW - PREVENTION
UR - http://www.scopus.com/inward/record.url?scp=85064082543&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0215075
DO - 10.1371/journal.pone.0215075
M3 - Article
C2 - 30958863
AN - SCOPUS:85064082543
VL - 14
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - 0215075
ER -
ID: 19357758