Rapid/sustained anti-anthrax passive immunity mediated by co-administration of Ad/AAV

Bishnu P. De, Neil R. Hackett, Ronald Crystal, Julie L. Boyer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 (AdαPA) and an AAV vector encoding an anti-PA monoclonal antibody (AAVrh.10αPA). As early as 1 day after co-administration of AdαPA and AAVrh.10αPA 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.

Original languageEnglish
Pages (from-to)203-209
Number of pages7
JournalMolecular Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Jan 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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