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

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 10(9) 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.

Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine

“…Adenovirus-vectored recombinant vaccines expressing a wide array of antigens have been constructed and protective immunity against different pathogens has been demonstrated in animal models [21][22][23][24][25]. In our research, we demonstrated the efficacy of using an adenovirus-based vaccine for single-time genetic vaccination that provided long-lasting protective immunity against botulism caused by botulinum neurotoxin type C.…”

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

“…Tan et al (30) first developed an adenovirus-based vaccine encoding humanized PA and evaluated the efficiency of this vaccine in a mouse model; the LT challenge showed that 72% of the mice survived 27 days after vaccination and 27% survived on day 11. Next, a nonhuman primate adenovirus, AdC7, was used as the vaccine vector in order to overcome the preexisting neutralizing antibodies against Ad5 in humans (31).…”

Anthrax

“…AdsechPA afforded approximately 2.7-fold more protection than the rPA vaccine against B. anthracis lethal toxin challenge four weeks after a single intramuscular administration, suggesting the potential of this vaccine to protect the civilian population against B. anthracis in response to a bioterrorism attack (Tan et al, 2003). Chimeric virus-like particles (VLPs), which are very effective at eliciting humoral as well as cellular immunity, were also tested.…”