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Nasal Immunization with Anthrax Protective Antigen Protein Adjuvanted with Polyriboinosinic–Polyribocytidylic Acid Induced Strong Mucosal and Systemic Immunities

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Purpose

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.

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Acknowledgments

This work was supported in part by funds from the General Research Fund from the Oregon State University and the Medical Research Foundation of Oregon. We would like to thank Julie Oughton in the Flow Cytometry and Cell Sorting Facilities at the Environmental Health Science Center of the Oregon State University for assistance in flow cytometry analyses.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, 97331, USA

    Brian R. Sloat & Zhengrong Cui

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Correspondence to Zhengrong Cui.

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Sloat, B.R., Cui, Z. Nasal Immunization with Anthrax Protective Antigen Protein Adjuvanted with Polyriboinosinic–Polyribocytidylic Acid Induced Strong Mucosal and Systemic Immunities. Pharm Res 23, 1217–1226 (2006). https://doi.org/10.1007/s11095-006-0206-9

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