title: Nasal immunization with the mixture of PA63, LF, and a PGA conjugate induced strong antibody responses against all three antigens.
abstract: A new generation anthrax vaccine is expected to target not only the anthrax protective antigen (PA) protein, but also other virulent factors of Bacillus anthracis. It is also expected to be amenable for rapid mass immunization of a large number of people. This study aimed to address these needs by designing a prototypic triantigen nasal anthrax vaccine candidate that contained a truncated PA (rPA63), the anthrax lethal factor (LF), and the capsular poly-gamma-D-glutamic acid (gammaDPGA) as the antigens and a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytodylic acid (poly(I:C)) as the adjuvant. This study identified the optimal dose of nasal poly(I:C) in mice, demonstrated that nasal immunization of mice with the LF was capable of inducing functional anti-LF antibodies (Abs), and showed that nasal immunization of mice with the prototypic triantigen vaccine candidate induced strong immune responses against all three antigens. The immune responses protected macrophages against an anthrax lethal toxin challenge in vitro and enabled the immunized mice to survive a lethal dose of anthrax lethal toxin challenge in vivo. The anti-PGA Abs were shown to have complement-mediated bacteriolytic activity. After further optimization, this triantigen nasal vaccine candidate is expected to become one of the newer generation anthrax vaccines.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Sloat
authors.forename: Dalia S
authors.initials: DS
authors.lastname: Shaker
authors.forename: Uyen M
authors.initials: UM
authors.lastname: Le
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology*; D001433:Bacteriolysis; D002460:Cell Line; D002470:Cell Survival; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage; D011099:Polyglutamic Acid / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C030325:anthrax toxin; D011099:Polyglutamic Acid; D003165:Complement System Proteins; D011070:Poly I-C