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

Abstract

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 highermore » 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.« less

Authors:

Xu, Yanqun ^[1]; He, Yong ^[1]; Momben-Abolfath, Sanaz ^[1]; Eller, Nancy ^[1]; Norton, Malgorzata ^[1]; Zhang, Pei ^[1]; Scott, Dorothy ^[1]; Struble, Evi Budo ^[1]

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+ Show Author Affiliations

1. U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Biologics Evaluation and Research. Office of Tissues and Advanced Therapies. Division of Plasma Protein Therapeutics. Lab. of Plasma Derivatives

Publication Date:

Mon Feb 01 00:00:00 EST 2021

Sponsoring Org.:

USDOE Office of Science (SC); FDA

OSTI Identifier:

1817039

Grant/Contract Number:  

SC0014664

Resource Type:

Accepted Manuscript

Journal Name:

Vaccines

Additional Journal Information:

Journal Volume: 9; Journal Issue: 2; Journal ID: ISSN 2076-393X

Publisher:

MDPI

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; anti-Zika antibodies; anti-Zika IgG; antibody dependent enhancement