title: Nasal immunization with a dual antigen anthrax vaccine induced strong mucosal and systemic immune responses against toxins and bacilli.
abstract: Anthrax-vaccine-adsorbed (AVA), the only anthrax vaccine licensed in the U.S., suffers from many major drawbacks. Therefore, there is a need to develop new generation anthrax vaccines that can be easily administered and induce strong immune responses not only against the anthrax toxins, but also against the toxin-producing vegetative anthrax bacilli. In the present study, we evaluated the feasibility of inducing strong mucosal and systemic immune responses against both anthrax toxins and bacilli after nasal immunization using a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytidylic acid (poly(I:C) or pI:C), as the adjuvant. We have shown that the capsular poly-gamma-D-glutamic acid (PGA) from bacillus was immunogenic when conjugated to a carrier protein and dosed intranasally to mice. We further demonstrated that nasal immunization with the PGA-carrier protein conjugate in combination with the anthrax protective antigen (PA) protein induced both anti-PGA and anti-PA immune responses in mouse sera and lung mucosal secretions. The anti-PA antibody (Ab) response was shown to have anthrax lethal toxin neutralization activity; and the anti-PGA Abs induced were able to activate complement and kill PGA-producing bacteria. These findings demonstrated that it is feasible to develop a novel dual-action nasal anthrax vaccine.
authors.affiliation: College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Sloat
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D002417:Cattle; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009666:Nose / Q000276:immunology*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology; D011119:Polynucleotides / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000906:Antibodies; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011119:Polynucleotides; C030325:anthrax toxin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; C049667:poly(rI).poly(dC); D012710:Serum Albumin, Bovine