Rapid/sustained anti-anthrax passive immunity mediated by co-administration of Ad/AAV. Academic Article uri icon

Overview

MeSH

  • Animals
  • Anthrax Vaccines
  • Antibodies, Monoclonal
  • Drug Administration Schedule
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Vaccines, Combined

MeSH Major

  • Adenoviridae
  • Anthrax
  • Bacillus anthracis
  • Dependovirus
  • Immunization, Passive

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 date

  • January 2008

has subject area

  • Adenoviridae
  • Animals
  • Anthrax
  • Anthrax Vaccines
  • Antibodies, Monoclonal
  • Bacillus anthracis
  • Dependovirus
  • Drug Administration Schedule
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Immunization, Passive
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Vaccines, Combined

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/sj.mt.6300344

PubMed ID

  • 18059375

Additional Document Info

start page

  • 203

end page

  • 209

volume

  • 16

number

  • 1