Thermostable vaccine compositions and methods of preparing same
Inventors
Hassett, Kimberly • Nandi, Pradyot • Brey, Robert N. • Carpenter, John • Randolph, Theodore
Assignees
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Publication Number
US-12097291-B2
Publication Date
2024-09-24
Expiration Date
Abstract
Compositions relating to thermostable vaccines and methods of preparing the same. Specifically, methods of preparing thermostable vaccines based on a recombinant ricin neurotoxin protein and uses of co-adjuvants to develop a composition capable of eliciting an immune response in a subject.
Core Innovation
The invention relates to thermostable, freeze-dried vaccine compositions that retain immunogenicity for recombinant protein antigens bound to aluminum-salt adjuvants. A frozen immunogenic composition is provided that comprises at least one aluminum-salt adjuvant and at least one antigen, where the immunogenic composition is frozen. The composition further includes a buffering agent comprising a buffering salt, selected from succinate, citrate, prolamine, arginine, glycine, histidine, and phosphate.
The frozen immunogenic composition includes at least one volatile salt selected from specified ammonium and amine salts and at least one glass forming agent selected from trehalose, sucrose, ficoll, dextran, maltotriose, lactose, mannitol and glycine, hydroxyethyl starch, and glycine. The use of these defined components is linked to maintaining immunogenicity and preventing aluminum particle aggregation while preserving particle size during freezing and lyophilization.
The compositions also include at least one immunologically-active co-adjuvant together with the antigen and aluminum-salt adjuvant. The disclosed embodiments report enhanced potency and neutralizing responses and stabilization of components upon thermal stress, including examples with immunostimulatory co-adjuvants such as CpG and TLR agonists including MPL/PHAD, as well as QS-21 and related saponin-based adjuvant systems.
Claims Coverage
The independent claim covers a frozen immunogenic composition defined by six required components: at least one aluminum-salt adjuvant, a buffering agent with buffering salts from a specified list, a volatile salt selected from a specified list, a glass forming agent selected from a specified list, at least one immunologically-active co-adjuvant, and at least one antigen, with the composition being frozen. The claim set refines this core concept through dependent claims that narrow specific adjuvant and excipient choices and add additional performance-related limitations tied to reduced aggregation and agglomeration upon reconstitution.
Frozen immunogenic composition with aluminum-salt adjuvant
A frozen immunogenic composition comprising at least one aluminum-salt adjuvant and at least one antigen, wherein the immunogenic composition is frozen.
Buffering agent with specified buffering salts
A frozen immunogenic composition further including at least one buffering agent wherein the buffering agent comprises a buffering salt, the at least one buffering agent selected from the group consisting of succinate, citrate, prolamine, arginine, glycine, histidine, and phosphate.
Volatile salt selected from specified ammonium/amine salts
A frozen immunogenic composition further including at least one volatile salt, the volatile salt selected from the group consisting of ammonium acetate, ammonium formate, ammonium carbonate, ammonium bicarbonate, triethylammonium acetate, triethylammonium formate, triethylammonium carbonate, trimethylamine acetate trimethylamine formate, trimethylamine carbonate, pyridinal acetate and pyridinal formate.
Glass forming agent selected from specified excipients/polymers/sugars
A frozen immunogenic composition further including at least one glass forming agent, the glass forming agent selected from the group consisting of trehalose, sucrose, ficoll, dextran, maltotriose, lactose, mannitol and glycine, hydroxyethyl starch, and glycine.
Immunologically-active co-adjuvant with antigen
A frozen immunogenic composition further comprising at least one immunologically-active co-adjuvant together with at least one antigen.
Essentially dried immunogenic composition reconstituted to show reduced aggregation
The frozen immunogenic composition provides that an essentially dried immunogenic composition is reconstituted, and the resulting adjuvant particles show reduced aggregation and agglomeration compared with a composition lacking a volatile salt.
Overall, the claim coverage centers on a frozen immunogenic composition requiring specified buffering salts, specified volatile salts, and specified glass forming agents, together with an aluminum-salt adjuvant, an immunologically-active co-adjuvant, and an antigen. Dependent limitations further narrow component selections and include a reconstitution-related limitation that the resulting adjuvant particles show reduced aggregation and agglomeration compared with a composition lacking a volatile salt.
Stated Advantages
Enhanced potency and neutralizing responses.
Stabilization of components upon thermal stress.
Reduced aggregation and agglomeration of adjuvant particles upon reconstitution compared with a composition lacking a volatile salt.
Documented Applications
Thermostable, freeze-dried vaccine compositions retaining immunogenicity for recombinant protein antigens bound to aluminum-salt adjuvants.
Vaccine immunogenicity and neutralization outcomes (including ricin neutralization) with storage at 4–60°C.
Use of immunostimulatory co-adjuvants including CpG and TLR agonists (including MPL/PHAD) and QS-21 in the frozen immunogenic composition.
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