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

Mol Ther. 2008 Jan;16(1):203-9. doi: 10.1038/sj.mt.6300344. Epub 2007 Dec 4.

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Animals
  • Anthrax / immunology
  • Anthrax / prevention & control*
  • Anthrax Vaccines / administration & dosage
  • Anthrax Vaccines / genetics
  • Anthrax Vaccines / immunology
  • Antibodies, Monoclonal / genetics
  • Bacillus anthracis / immunology*
  • Dependovirus / genetics
  • Dependovirus / immunology*
  • Drug Administration Schedule
  • Gene Transfer Techniques
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology
  • Humans
  • Immunization, Passive*
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / genetics
  • Vaccines, Combined / immunology

Substances

  • Anthrax Vaccines
  • Antibodies, Monoclonal
  • Vaccines, Combined