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PMID: 21304600 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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 ·Vol. 6 ·No. 1 ·2011-01-27 ·Pages e16532

Staats HF, Fielhauer JR, Thompson AL, Tripp AA, Sobel AE, Maddaloni M, Abraham SN, Pascual DW

Abstract

We previously reported that the immunogenicity of Hcβtre, 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 Hcβtre 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. New Zealand White or Dutch Belted rabbits were nasally immunized with Hcβtre or Hcβtre-Ad2F alone or combined with CT or C48/80, and serum samples were tested for the presence of Hcβtre-specific binding (ELISA) or BoNT/A neutralizing antibodies. Hcβtre-Ad2F nasally administered with CT induced serum anti-Hcβtre IgG ELISA and BoNT/A neutralizing antibody titers greater than those induced by Hcβtre + CT. C48/80 provided significant nasal adjuvant activity and induced BoNT/A-neutralizing antibodies similar to those induced by CT. Ad2F enhanced the nasal immunogenicity of Hcβtre, 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.

MeSH Terms
Adjuvants, Immunologic Administration, Intranasal Animals Antibodies, Neutralizing/biosynthesis Bacterial Vaccines/administration & dosage Botulinum Toxins, Type A/immunology Drug Delivery Systems/methods Mast Cells/immunology Mice Mucous Membrane/immunology Neurotoxins Rabbits Vaccines, Subunit/administration & dosage
Chemicals
Adjuvants, Immunologic Antibodies, Neutralizing Bacterial Vaccines Neurotoxins Vaccines, Subunit Botulinum Toxins, Type A
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Staats Herman F
Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America. herman.staats@duke.edu
Fielhauer Jeffrey R
Thompson Afton L
Tripp Alice A
Sobel Ashley E
Maddaloni Massimo
Abraham Soman N
Pascual David W
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0016532
Email
herman.staats@duke.edu
Published
2011-01-27
Epub
2011-00-27
Pages
e16532
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3029387
Subset
IM
Grants
NIAID NIH HHS · U54 AI06537 · United States
NIAID NIH HHS · R01 AI078938 · United States
NIAID NIH HHS · R01 AI064879 · United States
NIAID NIH HHS · R01 AI078938-04 · United States
NIDDK NIH HHS · R01 DK077159 · United States
NIAID NIH HHS · R21 AI059591 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0016532 PMC Full Text View journal details
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