Passive Immunotherapies Protect WRvFire and IHD-J-Luc Vaccinia Virus-Infected Mice from Lethality by Reducing Viral Loads in the Upper Respiratory Tract and Internal Organs▿
| Autor: | Michael Merchlinsky, Clement A. Meseda, Elisabeth Shotwell, Johan Lantto, Marina Zaitseva, Jerry P. Weir, Shantha Kodihalli, Henriette Schjønning Nielsen, Jody Manischewitz, Hana Golding, Lisa R. King, Senta M. Kapnick, John Scott |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Time Factors
viruses Immunology Respiratory System Vaccinia virus Biology Antibodies Viral Microbiology Virus Rodent Diseases chemistry.chemical_compound Mice Genes Reporter Virology medicine Vaccinia Smallpox Animals Whole Body Imaging Smallpox vaccine Luciferases Mice Inbred BALB C Staining and Labeling Immunization Passive Animal Structures Antibodies Monoclonal Viral Load medicine.disease Survival Analysis Recombinant Proteins Vaccination Disease Models Animal Viral replication chemistry Insect Science Immunoglobulin G Luminescent Measurements biology.protein Pathogenesis and Immunity Female Antibody Viral load |
| Popis: | Whole-body bioimaging was employed to study the effects of passive immunotherapies on lethality and viral dissemination in BALB/c mice challenged with recombinant vaccinia viruses expressing luciferase. WRvFire and IHD-J-Luc vaccinia viruses induced lethality with similar times to death following intranasal infection, but WRvFire replicated at higher levels than IHD-J-Luc in the upper and lower respiratory tracts. Three types of therapies were tested: licensed human anti-vaccinia virus immunoglobulin intravenous (VIGIV); recombinant anti-vaccinia virus immunoglobulin (rVIG; Symphogen, Denmark), an investigational product containing a mixture of 26 human monoclonal antibodies (HuMAbs) against mature virion (MV) and enveloped virion (EV); and HuMAb compositions targeting subsets of MV or EV proteins. Bioluminescence recorded daily showed that pretreatment with VIGIV (30 mg) or with rVIG (100 g) on day 2 protected mice from death but did not prevent viral replication at the site of inoculation and dissemination to internal organs. Compositions containing HuMAbs against MV or EV proteins were protective in both infection models at 100 g per animal, but at 30 g, only anti-EV antibodies conferred protection. Importantly, the t statistic of the mean total fluxes revealed that viral loads in surviving mice were significantly reduced in at least 3 sites for 3 consecutive days (days 3 to 5) postchallenge, while significant reduction for 1 or 2 days in any individual site did not confer protection. Our data suggest that reduction of viral replication at multiple sites, including respiratory tract, spleen, and liver, as monitored by whole-body bioluminescence can be used to predict the effectiveness of passive immunotherapies in mouse models. Following a massive vaccination campaign led by the World Health Organization, smallpox was declared eradicated in 1980. Vaccination of the general public in the United States was discontinued in 1972. However, in light of concerns that variola virus, the causative agent of smallpox, can be used as a bioterrorist weapon, strategies have been initiated worldwide, including in the United States, to develop medical countermeasures. The Preparedness and Response Program at the U.S. Centers for Disease Control and Prevention (CDC) recommended building stockpiles of smallpox vaccines for vaccination against smallpox, and anti-vaccinia virus immunoglobulin (VIG) for the management of serious adverse reactions to vaccination and postexposure treatment (5, 33). Currently, inoculation of military personnel with smallpox vaccine is a pol |
| Databáze: | OpenAIRE |
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