The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Indira U Mysorekar - One of the best experts on this subject based on the ideXlab platform.
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neutralizing human antibodies prevent zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor Barnes, Edgar Davidson, Indira U MysorekarAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease. This paper reports the isolation of human monoclonal antibodies from the B cells of eight subjects who had recovered from Zika virus infection. The authors determine the immune specificity and epitope recognition patterns of the antibodies and demonstrate that one of the pan-ZIKV neutralizing antibodies, termed ZIKV-117, can protect mice both post-infection and pre-infection, and provide Fetal protection in a pregnancy model. Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe Disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and Fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease, and reveal important determinants for structure-based rational vaccine design efforts.
Bin Cao - One of the best experts on this subject based on the ideXlab platform.
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zika virus infection during pregnancy in mice causes placental damage and Fetal demise
Cell, 2016Co-Authors: Jonathan J Miner, Bin Cao, Estefania Fernandez, Jennifer Govero, Amber M Smith, Omar H Cabrera, Charise Garber, Michelle Noll, Robyn S Klein, Kevin K NoguchiAbstract:Summary Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and Fetal Disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling ( Ifnar1 −/− ) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in Fetal demise that was associated with ZIKV infection of the placenta and Fetal brain. We identified ZIKV within trophoblasts of the maternal and Fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in Fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.
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Neutralizing human antibodies prevent Zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Bin CaoAbstract:Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe Disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and Fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-Fetal transmission, infection and Disease, and reveal important determinants for structure-based rational vaccine design efforts.Copyright © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Gopal Sapparapu - One of the best experts on this subject based on the ideXlab platform.
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neutralizing human antibodies prevent zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor Barnes, Edgar Davidson, Indira U MysorekarAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease. This paper reports the isolation of human monoclonal antibodies from the B cells of eight subjects who had recovered from Zika virus infection. The authors determine the immune specificity and epitope recognition patterns of the antibodies and demonstrate that one of the pan-ZIKV neutralizing antibodies, termed ZIKV-117, can protect mice both post-infection and pre-infection, and provide Fetal protection in a pregnancy model. Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe Disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and Fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease, and reveal important determinants for structure-based rational vaccine design efforts.
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Neutralizing human antibodies prevent Zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor BarnesAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease.
Estefania Fernandez - One of the best experts on this subject based on the ideXlab platform.
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neutralizing human antibodies prevent zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor Barnes, Edgar Davidson, Indira U MysorekarAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease. This paper reports the isolation of human monoclonal antibodies from the B cells of eight subjects who had recovered from Zika virus infection. The authors determine the immune specificity and epitope recognition patterns of the antibodies and demonstrate that one of the pan-ZIKV neutralizing antibodies, termed ZIKV-117, can protect mice both post-infection and pre-infection, and provide Fetal protection in a pregnancy model. Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe Disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and Fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease, and reveal important determinants for structure-based rational vaccine design efforts.
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Neutralizing human antibodies prevent Zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor BarnesAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease.
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zika virus infection during pregnancy in mice causes placental damage and Fetal demise
Cell, 2016Co-Authors: Jonathan J Miner, Bin Cao, Estefania Fernandez, Jennifer Govero, Amber M Smith, Omar H Cabrera, Charise Garber, Michelle Noll, Robyn S Klein, Kevin K NoguchiAbstract:Summary Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and Fetal Disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling ( Ifnar1 −/− ) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in Fetal demise that was associated with ZIKV infection of the placenta and Fetal brain. We identified ZIKV within trophoblasts of the maternal and Fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in Fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.
Trevor Barnes - One of the best experts on this subject based on the ideXlab platform.
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neutralizing human antibodies prevent zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor Barnes, Edgar Davidson, Indira U MysorekarAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease. This paper reports the isolation of human monoclonal antibodies from the B cells of eight subjects who had recovered from Zika virus infection. The authors determine the immune specificity and epitope recognition patterns of the antibodies and demonstrate that one of the pan-ZIKV neutralizing antibodies, termed ZIKV-117, can protect mice both post-infection and pre-infection, and provide Fetal protection in a pregnancy model. Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe Disease, including congenital birth defects during pregnancy1. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and Fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease, and reveal important determinants for structure-based rational vaccine design efforts.
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Neutralizing human antibodies prevent Zika virus replication and Fetal Disease in mice
Nature, 2016Co-Authors: Gopal Sapparapu, Estefania Fernandez, Nurgun Kose, Robin G Bombardi, Haiyan Zhao, Christopher A Nelson, Aubrey L Bryan, Trevor BarnesAbstract:Monoclonal Zika-virus-neutralizing human antibodies can protect against maternal–Fetal transmission, infection and Disease.