Stable anthrax vaccine formulations
Inventors
Assignees
Publication Number
US-8778359-B2
Publication Date
2014-07-15
Expiration Date
2029-07-30
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Abstract
Formulations of anthrax protective antigen are provided that are stable in storage for prolonged periods. Methods of using the formulations to prepare vaccine are also provided. Vaccines comprising the formulations are useful, for example, to protect against anthrax infection.
Core Innovation
The invention provides vaccine formulations containing Bacillus anthracis protective antigen (PA), such as recombinant PA (rPA), that exhibit significantly improved stability during storage. These formulations utilize specific amino acid-based buffers—particularly alanine, glycine, and proline—as excipients, either alone or in combination, at carefully controlled concentrations and pH ranges, often with additional salts, to enhance the longevity and biochemical integrity of the antigen.
The problem addressed is the lack of stability in recombinant PA-based anthrax vaccines, which has led to issues such as clinical trial holds due to degradation and loss of potency over time, especially at higher storage temperatures. Prior formulations, like the phosphate spike formulation, showed rapid degradation, prompting a need for improved vaccine stability to ensure effectiveness during storage and use.
Through systematic experimentation and biochemical/physicochemical assays, the present invention identifies formulation conditions—such as the use of an alanine buffer (generally 50 to 500 mM alanine, pH 6.2–8.0, with optional sodium phosphate and polysorbate 80)—that maintain PA in its native, immunogenic conformation for extended periods, with stability demonstrated at temperatures ranging from 2–8°C to below 25°C for up to two years. These formulations, when combined with pharmaceutically acceptable adjuvants like Alhydrogel, are suitable for preparing vaccines capable of both preventing and treating anthrax infection.
Claims Coverage
There is one independent claim covering the main inventive feature of a stable anthrax vaccine formulation. The patent also claims associated methods related to immunization, treatment, and immune response induction.
Stable vaccine formulation with alanine buffer and adjuvant
A stable vaccine for stimulating an immune response to a Bacillus anthracis protective antigen comprising: - A purified B. anthracis protective antigen protein; - An alanine formulation buffer; - A pharmaceutically acceptable adjuvant. The alanine formulation buffer may contain about 50 to 500 mM alanine and may further include glycine and/or proline, sodium phosphate, and polysorbate 80, within pH 6.2–8.0. The adjuvant can include alhydrogel, CpG, an immunostimulatory sequence (ISS), or calcium phosphate. The protective antigen may be produced from an asporogenic B. anthracis bacterium. The vaccine can include specific concentrations such as at least about 25 μg protective antigen protein and about 750 μg aluminum. The formulation may be in liquid solution or suspension.
Method of preventing or treating anthrax with stable vaccine
A method comprising administering a pharmaceutically effective amount of the stable vaccine formulation containing purified B. anthracis protective antigen protein, an alanine formulation buffer, and a pharmaceutically acceptable adjuvant to a subject in order to prevent or treat anthrax disease, including inhalation anthrax.
Method of inducing immune response with stable vaccine
A method comprising administering the vaccine formulation containing purified B. anthracis protective antigen protein, alanine formulation buffer, and pharmaceutically acceptable adjuvant to a subject to induce an immune response.
Vaccination method against anthrax using stable vaccine
A method comprising administering the vaccine formulation with purified B. anthracis protective antigen protein, alanine formulation buffer, and pharmaceutically acceptable adjuvant to a subject to vaccinate against anthrax.
In summary, the claims cover stable anthrax vaccine formulations utilizing an alanine-based buffer and adjuvant, as well as methods for using these vaccines to prevent, treat, and immunize subjects against anthrax.
Stated Advantages
The formulations improve the stability of Bacillus anthracis protective antigen (PA) during storage, exhibiting little or no decrease in activity, potency, or degradation over extended periods compared to control formulations.
Vaccines prepared with these formulations maintain immunogenicity and potency during prolonged storage at temperatures up to 25°C, for durations up to 2 years.
The alanine-based formulation consistently retains native protein conformation and functionality, resulting in higher and more stable immunological responses compared to other formulations.
The improved stability enables the production of efficient, reliable anthrax vaccines suitable for both pre- and post-exposure prophylaxis.
Documented Applications
Preparation and administration of vaccines for the prevention of anthrax infection, including pre-exposure prophylaxis.
Preparation and administration of vaccines for the treatment of anthrax infection (post-exposure prophylaxis).
Inducing an immune response in a subject against Bacillus anthracis protective antigen.
Production of antisera and purified anti-PA antibodies for use in treating exposure to anthrax or for diagnostic detection of anthrax toxin.
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