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Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface

Zika virus (ZIKV) infections have been associated with an increased incidence of severe microcephaly and other neurodevelopmental disorders in newborn babies. Passive immunization with anti-ZIKV neutralizing antibodies has the potential to become a feasible treatment or prophylaxis option during pre...

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Autores principales: Xu, Yanqun, He, Yong, Momben-Abolfath, Sanaz, Eller, Nancy, Norton, Malgorzata, Zhang, Pei, Scott, Dorothy, Struble, Evi Budo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916977/
https://www.ncbi.nlm.nih.gov/pubmed/33670199
http://dx.doi.org/10.3390/vaccines9020145
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author Xu, Yanqun
He, Yong
Momben-Abolfath, Sanaz
Eller, Nancy
Norton, Malgorzata
Zhang, Pei
Scott, Dorothy
Struble, Evi Budo
author_facet Xu, Yanqun
He, Yong
Momben-Abolfath, Sanaz
Eller, Nancy
Norton, Malgorzata
Zhang, Pei
Scott, Dorothy
Struble, Evi Budo
author_sort Xu, Yanqun
collection PubMed
description Zika virus (ZIKV) infections have been associated with an increased incidence of severe microcephaly and other neurodevelopmental disorders in newborn babies. Passive immunization with anti-ZIKV neutralizing antibodies has the potential to become a feasible treatment or prophylaxis option during pregnancy. Prior to clinical use, such antibodies should be assessed for their ability to block ZIKV passage to the fetus. We used human placental and mammalian cell monolayers that express FcRn and laboratory preparations of anti-ZIKV antibodies as a model system to investigate the disposition of ZIKV/antibody immune complexes (ICs) at the maternal-fetal interface. We further characterized solution properties of the ICs to evaluate whether these are related to in vitro effects. We found that both ZIKV and ZIKV envelope glycoprotein can enter and passage through epithelial cells, especially those that overexpress FcRn. In the presence of ZIKV antibodies, Zika virus entry was bimodal, with reduced entry at the lowest (0.3–3 ng/mL) and highest (µg/mL) antibody concentrations. Intermediate concentrations attenuated inhibition or enhanced viral entry. With respect to anti-ZIKV antibodies, we found that their degradation was accelerated when presented as ICs containing increased amounts of ZIKV immunogen. Of the two monoclonal antibodies tested, the preparation with higher aggregation also exhibited higher degradation. Our studies confirm that intact Zika virus and its envelope immunogen have the potential to enter and be transferred across placental and other epithelial cells that express FcRn. Presence of anti-ZIKV IgG antibodies can either block or enhance cellular entry, with the antibody concentration playing a complex role in this process. Physicochemical properties of IgG antibodies can influence their degradation in vitro.
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spelling pubmed-79169772021-03-01 Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface Xu, Yanqun He, Yong Momben-Abolfath, Sanaz Eller, Nancy Norton, Malgorzata Zhang, Pei Scott, Dorothy Struble, Evi Budo Vaccines (Basel) Article Zika virus (ZIKV) infections have been associated with an increased incidence of severe microcephaly and other neurodevelopmental disorders in newborn babies. Passive immunization with anti-ZIKV neutralizing antibodies has the potential to become a feasible treatment or prophylaxis option during pregnancy. Prior to clinical use, such antibodies should be assessed for their ability to block ZIKV passage to the fetus. We used human placental and mammalian cell monolayers that express FcRn and laboratory preparations of anti-ZIKV antibodies as a model system to investigate the disposition of ZIKV/antibody immune complexes (ICs) at the maternal-fetal interface. We further characterized solution properties of the ICs to evaluate whether these are related to in vitro effects. We found that both ZIKV and ZIKV envelope glycoprotein can enter and passage through epithelial cells, especially those that overexpress FcRn. In the presence of ZIKV antibodies, Zika virus entry was bimodal, with reduced entry at the lowest (0.3–3 ng/mL) and highest (µg/mL) antibody concentrations. Intermediate concentrations attenuated inhibition or enhanced viral entry. With respect to anti-ZIKV antibodies, we found that their degradation was accelerated when presented as ICs containing increased amounts of ZIKV immunogen. Of the two monoclonal antibodies tested, the preparation with higher aggregation also exhibited higher degradation. Our studies confirm that intact Zika virus and its envelope immunogen have the potential to enter and be transferred across placental and other epithelial cells that express FcRn. Presence of anti-ZIKV IgG antibodies can either block or enhance cellular entry, with the antibody concentration playing a complex role in this process. Physicochemical properties of IgG antibodies can influence their degradation in vitro. MDPI 2021-02-11 /pmc/articles/PMC7916977/ /pubmed/33670199 http://dx.doi.org/10.3390/vaccines9020145 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Yanqun
He, Yong
Momben-Abolfath, Sanaz
Eller, Nancy
Norton, Malgorzata
Zhang, Pei
Scott, Dorothy
Struble, Evi Budo
Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title_full Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title_fullStr Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title_full_unstemmed Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title_short Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface
title_sort entry and disposition of zika virus immune complexes in a tissue culture model of the maternal-fetal interface
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916977/
https://www.ncbi.nlm.nih.gov/pubmed/33670199
http://dx.doi.org/10.3390/vaccines9020145
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