Protective Effect of Anti-Phosphatidylserine Antibody in a Guinea Pig Model of Advanced Hemorrhagic Arenavirus Infection



John M. Thomas1, *, Philip E. Thorpe2
1 The University of Texas Rio Grande Valley Department of Biology; School of Medicine 1201 W. University Drive, Edinburg, Texas 78539, USA
2 The University of Texas Southwestern Medical Center Department of Pharmacology 2201 Inwood Road, Dallas, Texas 75390, USA


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© 2017 Thomas and Thorpe.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at The University of Texas – Rio Grande Valley* Department of Biology; School of Medicine 1201 W. University Blvd Edinburg, Texas 78539, USA, Tel: 956 665-7147; Fax: 956 665-3657; E-mails: john.thomas@utrgv.edu; thomjohn3@gmail.com


Abstract

Objective:

Host derived markers on virally infected cells or virions may provide targets for the generation of antiviral agents. Recently, we identified phosphatidylserine (PS) as a host marker of virions and virally-infected cells.

Methods and Materials:

Under normal physiological conditions, PS is maintained on the inner leaflet of the plasma membrane facing the cytosol. Following viral infection, activation or pre-apoptotic changes cause PS to become externalized. We have previously shown that bavituximab, a chimeric human-mouse antibody that binds PS complexed with β2-glycoprotein I (β2GP1), protected rodents against lethal Pichinde virus and cytomegalovirus infections.

Results:

Here, we determined the antiviral activity of a fully human monoclonal antibody, PGN632, that directly binds to PS. Treatment with PGN632 protected 20% of guinea pigs with advanced infections of the hemorrhagic arenavirus, Pichinde, from death. Combining PGN632 with ribavirin improved the antiviral activity of both agents, such that the combination rescued 50% of animals from death.

Conclusion:

The major mechanisms of action of PGN632 appear to be opsonization of virus and antibody-dependent cellular cytotoxicity of virally-infected cells. PS-targeting agents may have utility in the treatment of viral diseases.

Keywords: Anti-phosphatidylserine, Hemorrhagic arenavirus infection, Phosphatidylserine, Pichinde virus, Cellular cytotoxicity.