Challenge
Existing approved Anthrax vaccines are based on cell-free filtrates of disintegrated cells of Bacillus anthracis adsorbed onto an aluminium-hydrogel adjuvant. A number of side effects are attributed to these vaccines, including poor safety profile and a low immunogenicity necessitating repeated immunisation in order to confer protection. There is an urgent need for a new generation of anthrax vaccines that overcome these issues.
Anthrax recombinant protective antigen (rPA) is known to be the key immunogen in the existing vaccines which are protective against whole-organism challenge, and a lot of effort is currently made to develop such recombinant vaccines based on rPA. However, rPA is a very unstable protein, making transportation and stockpilingvery difficult. The objective of this study was to demonstrate that the stability of rPA can be improved, both in the absence and in the presence of an aluminium-hydrogel adjuvant by applying the ArestatT technology.
ArestatT solution
The ArestatT technology was first applied to the neat protein in the absence of an adjuvant. The native conformation of rPA depends on appropriate binding of two calcium ions within the structure of one of the four domains of the protein. Combination of several Arestat-TT formulation tools were used to produce a heat stable rPA vaccine. The tools employed ensured optimal binding of the calcium ions within the structure of rPA and exerted control over the proton exchange at the surface of the protein. The stabilised formulation showed a considerably improved stability over that in control formulations representing the current formulation candidates at optimal pH
Effect of ArestatT formulation on stability of aqueous rPA (100 g/ml) during storage. Stability is expressed in terms of the retention of the native RP-HPLC peak following storage at 25C
