Nasal immunization with anthrax protective antigen protein adjuvanted with polyriboinosinic-polyribocytidylic acid induced strong mucosal and systemic immunities.
OBJECTIVE
The current anthrax vaccine adsorbed (AVA) was originally licensed for the prevention of cutaneous anthrax infection. It has many drawbacks, including the requirement for multiple injections and subsequent annual boosters. Thus, an easily administrable and efficacious anthrax vaccine is needed to prevent the most lethal form of anthrax infection, inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein as the antigen and synthetic double-stranded RNA in the form of polyriboinosinic-polyribocytidylic acid (pI:C) as an adjuvant.


METHODS
Mice were nasally immunized with recombinant PA admixed with pI:C. The resulting PA-specific antibody responses and the lethal toxin neutralization activity were measured. Moreover, the effect of pI:C on dendritic cells (DCs) was evaluated both in vivo and in vitro.


RESULTS
Mice nasally immunized with rPA adjuvanted with pI:C developed strong systemic and mucosal anti-PA responses with lethal toxin neutralization activity. These immune responses compared favorably to that induced by nasal immunization with rPA adjuvanted with cholera toxin. Poly(I:C) enhanced the proportion of DCs in local draining lymph nodes and stimulated DC maturation.


CONCLUSIONS
This pI:C-adjuvanted rPA vaccine has the potential to be developed into an efficacious nasal anthrax vaccine.
Sloat
Brian R
BR
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Cui
Zhengrong
Z
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D020545:Respiratory Mucosa / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007071:Immunoglobulin A, Secretory; D011994:Recombinant Proteins; C030325:anthrax toxin; D011070:Poly I-C