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Anthrax sub-unit vaccine: The structural consequences of binding rPA83 to Alhydrogel (R)

Lookup NU author(s): Dr Andrei Soliakov, Ian Kelly, Professor Jeremy LakeyORCiD

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Abstract

An anthrax sub-unit vaccine, comprising recombinant Protective Antigen (rPA83) and aluminium hydroxide adjuvant (Alhydrogel (R)) is currently being developed. Here, a series of biophysical techniques have been applied to free and adjuvant bound antigen. Limited proteolysis and fluorescence identified no changes in rPA83 tertiary structure following binding to Alhydrogel and the bound rPA83 retained two structurally important calcium ions. For adsorbed rPA83, differential scanning calorimetry revealed a small reduction in unfolding temperature but a large decrease in unfolding enthalpy whilst urea unfolding demonstrated unchanged stability but a loss of co-operativity. Overall, these results demonstrate that interactions between rPA83 and Alhydrogel have a minimal effect on the folded protein structure and suggest that antigen destabilisation is not a primary mechanism of Alhydrogel adjuvancy. This study also shows that informative structural characterisation is possible for adjuvant bound sub-unit vaccines. (C) 2011 Elsevier B.V. All rights reserved.


Publication metadata

Author(s): Soliakov A, Kelly IF, Lakey JH, Watkinson A

Publication type: Article

Publication status: Published

Journal: European Journal of Pharmaceutics and Biopharmaceutics

Year: 2012

Volume: 80

Issue: 1

Pages: 25-32

Print publication date: 21/09/2011

ISSN (print): 0939-6411

ISSN (electronic): 1873-3441

Publisher: Elsevier BV

URL: http://dx.doi.org/10.1016/j.ejpb.2011.09.009

DOI: 10.1016/j.ejpb.2011.09.009


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Funding

Funder referenceFunder name
BBRSC
1UC1AI67223-01NIH NIAID
N01 AI-25492NIH NIAID
N01 AI-30052NIH NIAID

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