RESEARCH ARTICLE
Protective Effect of Anti-Phosphatidylserine Antibody in a Guinea Pig Model of Advanced Hemorrhagic Arenavirus Infection
John M. Thomas1, *, Philip E. Thorpe2
Article Information
Identifiers and Pagination:
Year: 2017Volume: 11
First Page: 303
Last Page: 315
Publisher ID: TOMICROJ-11-303
DOI: 10.2174/1874285801711010303
Article History:
Received Date: 01/08/2017Revision Received Date: 01/11/2017
Acceptance Date: 11/11/2017
Electronic publication date: 30/11/2017
Collection year: 2017

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.
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.