Original article
Combination therapy of vaccinia virus infection with human anti-H3 and anti-B5 monoclonal antibodies in a small animal model
Megan M McCausland, Mohammed Rafii-El-Idrissi Benhnia, Lindsay Crickard, John Laudenslager, Steven W Granger, Tomoyuki Tahara, Ralph Kubo, Lilia Koriazova, Shinichiro Kato, Shane Crotty
Corresponding author name: Shane Crotty
Corresponding author e-mail: shane@liai.org
Citation: Antiviral Therapy 2010; 15:661-675
doi: 10.3851/IMP1573
Date published online: 25 June 2010
Abstract
Background: Treatment of rare severe side effects of vaccinia virus (VACV) immunization in humans is currently very challenging. VACV possesses two immunologically distinct virion forms in vivo – intracellular mature virion (MV, IMV) and extracellular virion (EV, EEV).
Methods: Antibody-mediated therapeutic efficacy was determined against VACV infection in a small animal model of progressive vaccinia. The model consisted of severe combined immunodeficiency mice infected with VACV New York City Board of Health vaccine strain and treated with monoclonal antibodies (mAbs).
Results: Here, we show that combination therapy with two fully human mAbs against an immunodominant MV antigen, H3 (H3L), and an EV antigen, B5 (B5R), provides significantly better protection against disease and death than either single human monoclonal or human vaccinia immune globulin, the currently licensed therapeutic for side effects of smallpox vaccination.
Conclusions: The preclinical studies validate that this combination of mAbs against H3 and B5 is a promising approach as a poxvirus infection treatment for use in humans.