#Monoclonal #antibodies with neutralizing activity and Fc-effector functions against the #Machupo virus glycoprotein (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Monoclonal antibodies with neutralizing activity and Fc-effector functions against the Machupo virus glycoprotein

Fatima Amanat, James Duehr, Cheng Huang, Slobodan Paessler, Gene Tan, Florian Krammer

DOI: 10.1128/JVI.01741-19

 

ABSTRACT

Machupo virus (MACV), the causative agent of Bolivian hemorrhagic fever (BHF), is a New World arenavirus that was first isolated in Bolivia from a human spleen in 1963. Due to the lack of a specific vaccine or therapy, this virus is considered a major risk to public health and is classified as a Category A Priority Pathogen by the US National Institutes of Health. In this study, we used DNA vaccination against the MACV glycoprotein precursor complex (GPC) and murine hybridoma technology to generate 25 mouse monoclonal antibodies (mAbs) against the GPC of MACV. Out of 25, five mAbs were found to have potent neutralization activity in vitro against a recombinant vesicular stomatitis virus expressing MACV GPC (VSV-MACV) as well as authentic MACV. Furthermore, the five neutralizing mAbs exhibited strong antibody-dependent cellular cytotoxicity (ADCC) activity in a reporter assay. When tested in vivo using VSV-MACV in a Stat2-/- mouse model, three mAbs significantly lowered viral loads in the spleen. Our work provides valuable insights into epitopes targeted by neutralizing antibodies that could be potent targets for vaccines and therapeutics, and shed light towards the importance of effector functions in immunity against MACV.

 

Significance

MACV infections are a significant public health concern and lead to high case fatality rates. No specific treatment or vaccine for MACV infections exist. However, cases of Junin virus infection, a related virus, can be treated with convalescent serum. This indicates, that a mAb-based therapy for MACV could be effective. Here, we describe several mAbs that neutralize MACV and could be used for this purpose.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Arenavirus; Machupo virus; Monoclonal antibodies; Bolivian Hemorrhagic Fever.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.