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

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant... Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions Allan Watkinson a * , Andrei Soliakov b , Ashok Ganesan c , Karie Hirst d , Chris LeButt e , Kelly Fleetwood f , Peter C. Fusco d , Thomas R. Fuerst d and Jeremy H. Lakey b PharmAthene UK Ltd., Billingham, United Kingdom a Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, United Kingdom b XstalBio Ltd., Glasgow, United Kingdom c PharmAthene, Inc., Annapolis, Maryland, USA d Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom e Quantics, Edinburgh, United Kingdom f 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

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

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

Clinical and Vaccine Immunology , Volume 20 (11): 1659 – Nov 1, 2013

Abstract

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions Allan Watkinson a * , Andrei Soliakov b , Ashok Ganesan c , Karie Hirst d , Chris LeButt e , Kelly Fleetwood f , Peter C. Fusco d , Thomas R. Fuerst d and Jeremy H. Lakey b PharmAthene UK Ltd., Billingham, United Kingdom a Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, United Kingdom b XstalBio Ltd., Glasgow, United Kingdom c PharmAthene, Inc., Annapolis, Maryland, USA d Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom e Quantics, Edinburgh, United Kingdom f 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.

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References (58)

Publisher
American Society For Microbiology
Copyright
Copyright © 2013 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.00320-13
pmid
23986317
Publisher site
See Article on Publisher Site

Abstract

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions Allan Watkinson a * , Andrei Soliakov b , Ashok Ganesan c , Karie Hirst d , Chris LeButt e , Kelly Fleetwood f , Peter C. Fusco d , Thomas R. Fuerst d and Jeremy H. Lakey b PharmAthene UK Ltd., Billingham, United Kingdom a Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, University of Newcastle, Newcastle-upon-Tyne, United Kingdom b XstalBio Ltd., Glasgow, United Kingdom c PharmAthene, Inc., Annapolis, Maryland, USA d Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom e Quantics, Edinburgh, United Kingdom f 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.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Nov 1, 2013

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