Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits

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Abstract

Background: We previously reported that the immunogenicity of Hcbtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was performed to determine if Ad2F would enhance the nasal immunogenicity of Hcbtre in rabbits, an animal model with a nasal cavity anatomy similar to humans. Since CT is not safe for human use, we also tested the adjuvant activity of compound 48/80 (C48/80), a mast cell activating compound previously determined to safely exhibit nasal adjuvant activity in mice. Methods: New Zealand White or Dutch Belted rabbits were nasally immunized with Hcbtre or Hcbtre-Ad2F alone or combined with CT or C48/80, and serum samples were tested for the presence of Hcbtre-specific binding (ELISA) or BoNT/A neutralizing antibodies. Results: Hcbtre-Ad2F nasally administered with CT induced serum anti-Hcbtre IgG ELISA and BoNT/A neutralizing antibody titers greater than those induced by Hcbtre + CT. C48/80 provided significant nasal adjuvant activity and induced BoNT/Aneutralizing antibodies similar to those induced by CT. Conclusions: Ad2F enhanced the nasal immunogenicity of Hcbtre, and the mast cell activator C48/80 was an effective adjuvant for nasal immunization in rabbits, an animal model with a nasal cavity anatomy similar to that in humans. © 2011 Staats et al.

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Staats, H. F., Fielhauer, J. R., Thompson, A. L., Tripp, A. A., Sobel, A. E., Maddaloni, M., … Pascual, D. W. (2011). Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits. PLoS ONE, 6(1). https://doi.org/10.1371/journal.pone.0016532

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