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Antiviral research2019; 174; 104666; doi: 10.1016/j.antiviral.2019.104666

Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junín virus.

Abstract: Argentine haemorrhagic fever (AHF) is a rodent-borne disease with a lethality as high as ~30%, which is caused by the New World arenavirus, Junín virus (JUNV). It was once a major epidemic in South America and puts millions of people in Argentina at risk. Here, we aimed to develop horse antibodies or antibody fragments against JUNV. Before preparing the horse antibodies, a strategy to efficiently generate horse antisera was established based on comparisons among immunogens and immunization methods in both mice and horses. Antisera against JUNV were finally obtained by vaccinating horses with vesicular stomatitis virus pseudotypes bearing JUNV GP. The horse antibodies IgG and F(ab')2 were subsequently demonstrated to effectively neutralize vesicular stomatitis virus pseudotypes bearing JUNV GP and to show some cross-neutralization against pathogenic New World arenaviruses. Further research revealed that Asp123 on GP1 is an important site for the binding of antibodies targeting mainly JUNV GP1 for neutralization. Collectively, this study presents an efficient strategy to develop horse antisera against JUNV and provides GP1-specific horse antibodies as potential therapeutics for AHF.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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Publication Date: 2019-11-21 PubMed ID: 31760108PubMed Central: PMC7114285DOI: 10.1016/j.antiviral.2019.104666Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study aimed to develop horse antibodies against Junín virus (JUNV), which causes the potentially lethal Argentine haemorrhagic fever (AHF). Researchers established an effective method to generate horse antibodies, demonstrated their capacity to neutralize JUNV, and identified a key binding site on the virus’s GP1 protein.

Development of Horse Antibodies Against Junín Virus

  • The research aimed at developing horse antibodies that could treat or combat Argentine Hemorrhagic Fever (AHF), a potentially deadly disease caused by the Junín virus. This virus, mainly spreading through rodents, had caused major epidemics in South America and still poses a threat to millions of people in Argentina.
  • Before commencing the process of preparing horse antibodies, the researchers set up a strategy to create horse antisera efficiently. This strategy was designed based on comparisons among immunogens and immunization practices in both mice and horses.

Methodology and Findings

  • The research team used vesicular stomatitis virus pseudotypes bearing the Junín virus GP to vaccinate horses, subsequently obtaining antisera against the virus.
  • They later tested the “IgG” and “F(ab’)” horse antibodies obtained from the antisera and found that these could effectively neutralize the vesicular stomatitis virus pseudotypes bearing the Junín virus GP.
  • In the process, the antibodies also exhibited some cross-neutralization properties against other pathogenic New World arenaviruses.

Identification of Key Binding Site

  • The research took a step further by identifying an essential site on GP1, a protein associated with the Junín virus, which the antibodies target for neutralization. This vital site was identified as Asp123.
  • Understanding the specific binding site can prove critical in designing and strategizing therapeutic interventions targeting the Junín virus.

Conclusion of the Study

  • The study delivered an efficient method of developing horse antisera against the Junín virus and potentially other similar viruses.
  • The discovery of GP1-specific horse antibodies with their known binding site sets the stage for these to be used as potential therapeutics in the treatment of AHF.

Cite This Article

APA
Pan X, Wu Y, Wang W, Zhang L, Xiao G. (2019). Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junín virus. Antiviral Res, 174, 104666. https://doi.org/10.1016/j.antiviral.2019.104666

Publication

Antiviral research
ISSN: 1872-9096
NlmUniqueID: 8109699
Country: Netherlands
Language: English
Volume: 174
Pages: 104666

Researcher Affiliations

Pan, Xiaoyan
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Wu, Yan
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
Wang, Wei
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China.
Zhang, Leike
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China.
Xiao, Gengfu
  • State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100039, China. Electronic address: xiaogf@wh.iov.cn.

MeSH Terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cross Reactions
  • Female
  • Hemorrhagic Fever, American / immunology
  • Hemorrhagic Fever, American / veterinary
  • Horses / immunology
  • Immunoglobulin Fragments / immunology
  • Junin virus / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests

Conflict of Interest Statement

Declaration of competing interest The authors declare no competing financial interests.

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