Biophysical characterization and immunization studies of dominant negative inhibitor (DNI), a candidate anthrax toxin subunit vaccine

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Authors
Iyer, Vidyashankara
Hu, Lei
Schante, Carole E.
Vance, David
Chadwick, Chrystal
Jain, Nishant Kumar
Brey, Robert N.
Joshi, Sangeeta B.
Volkin, David B.
Andra, Kiran K.
Issue Date
2013-11
Type
Article
Language
en_US
Keywords
Dominant-negative inhibitor , Vaccine , Aluminum hydroxide , Immunogenicity , Accelerated stability , Biophysical characterization
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Abstract

Dominant negative inhibitor (DNI) is a translocation-deficient homolog of recombinant protective antigen of Bacillus anthracis that is a candidate for a next generation anthrax vaccine. This study demonstrates that the biophysical characteristics of the DNI protein stored in lyophilized form at 4 degrees C for 8 y were similar to recombinant protective antigen (rPA). To provide information on the accelerated stability of DNI, samples in the lyophilized form were subjected to thermal stress (40 and 70 degrees C for up to 4 weeks) and thoroughly evaluated using various biophysical and chemical characterization techniques. Results demonstrate preserved structural stability of the DNI protein under extreme conditions, suggesting long-term stability can be achieved for a vaccine that employs DNI, as desired for a biodefense countermeasure. Furthermore, the biological activity of the stressed DNI bound to the adjuvant Alhydrogel (R) was evaluated in mice and it was found that the immunogenicity of DNI was not affected by thermal stress.

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Iyer, Vidyashankara; Hu, Lei; Schante, Carole E.; Vance, David; Chadwick, Chrystal; Jain, Nishant Kumar; Brey, Robert N.; Joshi, Sangeeta B.; Volkin, David B.; Andra, Kiran K.; Bann, James G.; Mantis, Nicholas J.; Middaugh, C. Russell. 2013. Biophysical characterization and immunization studies of dominant negative inhibitor (DNI), a candidate anthrax toxin subunit vaccine. Human Vaccines & Immunotherapeutics, vol. 9:no. 11:ppg. 2362-2370
Publisher
Landes Bioscience
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DOI
ISSN
2164-5515
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