Protective Immunity Evoked Against Anthrax Lethal Toxin after a Single Intramuscular Administration of an Adenovirus-Based Vaccine Encoding Humanized Protective Antigen

Yadi Tan, Neil R. Hackett, Julie L. Boyer, Ronald G. Crystal

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Because of the need to develop a vaccine to rapidly protect the civilian population in response to a bioterrorism attack with Bacillus anthracis, we designed AdsechPA, a replication-deficient human serotype 5 adenovirus encoding B. anthracis protective antigen (PA) with codons optimized for expression in mammalian cells. With a single intramuscular administration to mice of 109 particle units of AdsechPA, a dose that can be scaled to human use, anti-PA antibodies were evoked more rapidly and at a higher level than with a single administration of the new U.S. military recombinant PA/Alhydrogel vaccine. Importantly, AdsechPA afforded approximately 2.7-fold more protection than the recombinant PA vaccine against B. anthracis lethal toxin challenge 4 weeks after a single vaccination. Even at 11 days postvaccination, AdsechPA provided some survival benefit, whereas the rPA/Alhydrogel vaccine provided none. In the context that equivalent human doses of Ad vectors have already been demonstrated to be safe in humans, a single administration of AdsechPA may provide the means to rapidly protect the civilian population against B. anthracis in response to a bioterrorism attack.

Original languageEnglish
Pages (from-to)1673-1682
Number of pages10
JournalHuman gene therapy
Volume14
Issue number17
DOIs
Publication statusPublished - 20 Nov 2003

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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