title: Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.
abstract: Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Shipo
authors.initials: S
authors.lastname: Wu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Song
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Yi
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
authors.forename: Jianqin
authors.initials: J
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.forename: Lihua
authors.initials: L
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D014614:Vaccines, Synthetic; C030325:anthrax toxin