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Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Lookup NU author(s): Dr Andrei Soliakov, Professor Jeremy Lakey

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Abstract

Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.


Publication metadata

Author(s): Watkinson A, Soliakov A, Ganesan A, Hirst K, LeButt C, Fleetwood K, Fusco PC, Fuerst TR, Lakey JH

Publication type: Article

Publication status: Published

Journal: Clinical and Vaccine Immunology

Year: 2013

Volume: 20

Issue: 11

Pages: 1659-1668

Print publication date: 01/11/2013

Online publication date: 28/08/2013

Acceptance date: 16/08/2013

ISSN (print): 1556-6811

ISSN (electronic): 1556-679X

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/CVI.00320-13

DOI: 10.1128/CVI.00320-13


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