Rapid/sustained anti-anthrax passive immunity mediated by co-administration of Ad/AAV.
Achieving both immediate and sustained protection against diseases caused by bacterial toxins and extracellular pathogens is a challenge in developing biodefense 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 (AdalphaPA) and an AAV vector encoding an anti-PA monoclonal antibody (AAVrh.10alphaPA). As early as 1 day after co-administration of AdalphaPA and AAVrh.10alphaPA 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.
De
Bishnu P
BP
Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York, USA.
Hackett
Neil R
NR
Crystal
Ronald G
RG
Boyer
Julie L
JL
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics; D001408:Bacillus anthracis / Q000276:immunology*; D000229:Dependovirus / Q000235:genetics / Q000276:immunology*; D004334:Drug Administration Schedule; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D022122:Anthrax Vaccines; D000911:Antibodies, Monoclonal; D017778:Vaccines, Combined