Lyophilized and stabilized live attenuated formulated vaccine against tularemia
Inventors
CARSON, Kenneth H. • CABINESS, Spring M. • DE LOS SANTOS, Amy M. • Klose, Karl
Assignees
Southwest Research Institute SwRI
Publication Number
US-12343431-B2
Publication Date
2025-07-01
Expiration Date
2043-11-07
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Abstract
A lyophilized stabilized formulation containing a live attenuated vaccine strain against tularemia. The method includes supplying the immunogenic agent comprising Fn-igIDOAgFTT and subjecting the immunogenic agent to lyophilization and recovering a lyophilized and stabilized form of such immunogenic agent.
Core Innovation
The invention is directed to a lyophilized stabilized formulation containing a live attenuated vaccine strain against tularemia. Specifically, the immunogenic agent comprises Fn-iglD OAgFTT, an engineered form of Francisella novicida (Fn) that is avirulent in humans and configured to express the lipopolysaccharide O-Antigen from the more virulent Francisella tularensis subsp. tularensis (Ftt). The vaccine strain KKF768 (Fn-iglD OAgFTT) expresses this OAgFTT attached to its LPS, conferring immunogenic properties.
The background identifies tularemia as caused by Francisella tularensis, a category A selected agent with high virulence, posing a threat both to the public and warfighters. The only current vaccine, the Live Vaccine Strain (LVS), is an attenuated F. tularensis subsp. holarctica strain lacking in genetic stability and safety, rendering it a poor candidate for FDA approval. There remains a need for an FDA-approved formulated vaccine against F. tularensis that permits intradermal delivery, provides high protective immunity, and ensures storage stability.
The invention solves this problem by employing a stabilized formulation using a stabilizer mix of 10% Trehalose, 5% Mannitol, and 0.2% Cysteine as cryoprotectants, followed by a specific lyophilization process. The lyophilization involves controlled cooling from 5°C to −45°C to −35°C at defined rates, primary and secondary drying phases with specified temperatures and pressures, and final vial stoppering. This process results in a viable, stabilized, lyophilized vaccine formulation that shows protective immunity upon intradermal administration and improved storage properties.
Claims Coverage
The patent contains one independent claim focusing on a method of producing a lyophilized and stabilized immunogenic agent for prevention or treatment of Francisella tularensis infection. The claim encompasses multiple inventive features relating to the vaccine strain formulation, stabilizer composition, and lyophilization process parameters.
Use of Fn-iglD OAgFTT in a specific stabilizer mix
The immunogenic agent comprising the live attenuated vaccine strain Fn-iglD OAgFTT is supplied in a stabilizer mix consisting of 10.0% Trehalose (w/v), 5.0% Mannitol (w/v), and 0.2% Cysteine (w/v) as cryoprotectants.
Controlled lyophilization process with defined temperature and pressure parameters
The immunogenic agent is subjected to lyophilization involving: starting at 5.0°C and freezing to a temperature between −45.0°C and −35.0°C at a cooling rate of 55.0°C to 65.0°C per hour, maintaining that temperature for 2.5 to 3.5 hours; primary drying at −35.0°C to −25.0°C under 0.45 mbar to 0.55 mbar pressure for 40 to 55 hours; and secondary drying at 0°C to 10°C at a heating rate of 25°C to 35°C per hour, followed immediately by nitrogen purging and vial stoppering.
The inventive features include the use of a live attenuated vaccine strain Fn-iglD OAgFTT in a specific stabilizer composition combined with a detailed, controlled lyophilization protocol that preserves viability and stability, resulting in a lyophilized vaccine suitable for use against Francisella tularensis infections.
Stated Advantages
Provides a stabilized lyophilized formulation of the live attenuated vaccine strain against tularemia with improved storage stability.
Enables intradermal delivery of the vaccine.
Confers relatively high protective immunity upon vaccination and booster administration.
Documented Applications
Prevention or treatment of infection by Francisella tularensis in animals, including humans.
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