A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos.

Abstract

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine.

• Authors: Cui Li, Fei Gao, Lei Yu, Ruoke Wang, Yisheng Jiang, Xuanling Shi, Chibiao Yin, Xiaoping Tang, Fuchun Zhang, Zhiheng Xu, Linqi Zhang
• Journal: Cell reports (Cell Rep) Vol. 23 Issue 5 Pg. 1424-1434 (05 01 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 29719255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Neutralizing (pharmacology)
• Antibodies, Viral (pharmacology)
• Disease Models, Animal
• Embryo, Mammalian (embryology, pathology)
• Embryonic Development (drug effects)
• Female
• Humans
• Mice
• Mice, Inbred ICR
• Microcephaly (drug therapy, metabolism, pathology)
• Pregnancy
• Pregnancy Complications, Infectious (drug therapy, metabolism, pathology)
• Zika Virus (metabolism)
• Zika Virus Infection (drug therapy, metabolism, pathology)