Journal
MOLECULAR THERAPY
Volume 16, Issue 1, Pages 203-209Publisher
CELL PRESS
DOI: 10.1038/sj.mt.6300344
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U54AI057158, R01AI055844] Funding Source: NIH RePORTER
- NIAID NIH HHS [U54 AI057158, R01 AI 55844] Funding Source: Medline
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Achieving both immediate and sustained protection against diseases caused by bacterial toxins and extracellular pathogens is a challenge in developing bio-defense therapeutics. We hypothesized that a single co-administration of an adenovirus (Ad) vector and an adeno-associated virus (AAV) vector, both expressing a pathogen-specific monoclonal antibody, would provide rapid, persistent passive immunotherapy against the pathogen. In order to test this strategy, we used the lethal toxin of Bacillus anthracis as a target of a monoclonal antibody directed against the protective antigen (PA) component of the toxin, using co-administration of an Ad vector encoding an anti-PA monoclonal antibody (Ad alpha PA) and an AAV vector encoding an anti-PA monoclonal antibody (AAVrh. 10 alpha PA). As early as 1 day after co-administration of Ad alpha PA and AAVrh. 10 alpha PA to mice, serum anti-PA antibody levels were detectable, and were sustained through 6 months. Importantly, animals that received both vectors were protected against toxin challenge as early as 1 day after administration and throughout the 6 month duration of the experiment. These data provide a new paradigm of genetic passive immunotherapy by co-administration of Ad and AAV vectors, each encoding a pathogen-specific monoclonal antibody, as an effective approach for both rapid and sustained protection against a bio-terror attack.
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