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EP-4735041-A1 - STABILIZER COMPOSITION FOR IMMUNOGENIC COMPOSITIONS, STABILIZED IMMUNOGENIC COMPOSITIONS, METHODS AND APPLICATIONS THEREOF

EP4735041A1EP 4735041 A1EP4735041 A1EP 4735041A1EP-4735041-A1

Abstract

The present disclosure relates to compositions and methods for stabilizing immunogenic compositions. Particularly, the present disclosure provides an easy to prepare and economical stabilizer composition comprising components selected from a group comprising sugar(s), amino acid(s), protein(s) or peptide(s), mineral salt(s); and buffer(s) of any combination thereof. Further provided herein is a stabilized immunogenic composition comprising the stabilizer composition in combination with antigen(s) or pathogen(s) of interest? The present disclosure additionally provides methods for preparing the stabilizer composition and the stabilized immunogenic composition and applications thereof. The stabilizer composition of the present disclosure is easy to prepare and store. The stabilizer composition further confers long-term stability to immunogenic compositions, at various storage temperatures.

Inventors

  • PERNAMALLUR, Sivakumar Ayyaswamy
  • MATUR, RAMESH VENKAT
  • KANNACHARI, Harish
  • MANTENA, Narender Dev
  • DATLA, Mahima

Assignees

  • Biological E Limited

Dates

Publication Date
20260506
Application Date
20240627

Claims (20)

  1. 1. A stabilizer composition for preparation of lyophilized viral vaccines, comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein(s) or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).
  2. 2. The stabilizer composition as claimed in claim 1, wherein the sugar(s) is present at a concentration of about 1 % w/v to about 15 % w/v; the amino acid(s) is present at a concentration of about 0.01 % w/v to about 10 % w/v; the protein(s) or peptide(s) is present at a concentration of about 0.05% w/v to about 10% w/v; and/or the mineral salt(s) is present at a concentration of about 0.1 % w/v to about 10% w/v.
  3. 3. The stabilizer composition as claimed in any one of claims 1 to 2, wherein the sugar(s) is selected from a group comprising monosaccharide(s), disaccharide(s), polysaccharide(s), sugar alcohol(s), and their derivatives or any combination thereof.
  4. 4. The stabilizer composition as claimed in claim 3, wherein the monosaccharide(s) is selected from a group comprising fructose, galactose, glucose, D-mannose, sorbose, and their derivatives or any combination thereof; the disaccharide(s) is selected from a group comprising lactose, maltose, trehalose/ trehalose dihydrate, cellobiose, and their derivatives or any combination thereof; the polysaccharide(s) is selected from a group comprising raffinose, melezitose, maltodextrins, dextrans, starches, and their derivatives or any combination thereof; and the sugar alcohol(s) is selected from a group comprising mannitol, xylitol, maltitol, lactitol, sorbitol, myoinositol, and their derivatives or any combination thereof.
  5. 5. The stabilizer composition as claimed in any one of claims 1-4, wherein the sugar(s) is a combination of sorbitol and trehalose/ trehalose dihydrate; wherein sorbitol and trehalose/trehalose dihydrate are each present at a concentration of about 1 % w/v to about 10 % w/v.
  6. 6. The stabilizer composition as claimed in any one of claims 1-5, wherein the amino acid(s) is a non-acidic amino acid(s); wherein the amino acid(s) is selected from a group comprising Alanine, Arginine, Asparagine, Cysteine, Glutamine, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine, and their salts, any modification or derivative thereof or any combination thereof.
  7. 7. The stabilizer composition as claimed in claim 6, wherein the amino acid(s) comprise proline and glycine, their salts, any modification or derivative thereof, wherein glycine and proline are each present at a concentration in the range of about 0.1 % w/v to about 5 % w/v.
  8. 8. The stabilizer composition as claimed in claim 7, wherein the stabilizer composition further comprises one or more amino acid(s) selected from a group comprising alanine, arginine/arginine monohydrochloride, histidine, and their salts, any modification or derivative thereof, wherein alanine, arginine/arginine monohydrochloride, or histidine are each present at a concentration in a range of about 0.01% w/v to about 5% w/v.
  9. 9. The stabilizer composition as claimed in any one of claims 1-8, wherein the protein(s) or peptide(s) is selected from a group comprising hydrolyzed gelatin, lactalbumin, lactalbumin hydrolysate, human serum albumin (HSA), a recombinant human serum albumin (rHSA), and other serum albumins or albumin gene family member or any combination thereof.
  10. 10. The stabilizer composition as claimed in claims 9, wherein the protein or peptide is hydrolyzed gelatin and human serum albumin (HSA); wherein the hydrolyzed gelatin is present at a concentration of about 0.5 % w/v to about 10 % w/v; and/or wherein the HSA is present at a concentration of about 0.05 % w/v to about 2 % w/v.
  11. 11. The stabilizer composition as claimed in any one of claims 1-10, wherein the mineral salt(s) is selected from a group comprising zinc sulphate, magnesium sulphate, zinc chloride, and magnesium chloride or any combination thereof.
  12. 12. The stabilizer composition as claimed in any of the claims 1-11, wherein the mineral salt(s) is magnesium sulphate heptahydrate; and wherein the magnesium sulphate heptahydrate is present at a concentration of about 0.1 % w/v to about 10 % w/v.
  13. 13. The stabilizer composition as claimed in any one of claims 1-12, wherein the buffer(s) is selected from a group comprising phosphate buffers such as phosphate buffered saline (PBS), acetate buffers, benzoate buffer, citrate buffers, lactate buffers, maleate buffers, tartrate buffers, histidine buffer, succinate buffer, phosphate - citrate buffer, HEPES buffer, and borate buffer or any combination thereof.
  14. 14. The stabilizer composition as claimed in claim 13, wherein the buffer(s) is phosphate - citrate buffer; wherein the phosphate concentration in the buffer is in the range of about 5 mM to about 15 mM and the citrate concentration in the buffer is in the range of about 0.5 mM to about 5 mM.
  15. 15. The stabilizer composition as claimed in any one of claims 1-14, wherein the pH of the stabilizer composition is in the range of about 5 to about 8.
  16. 16. The stabilizer composition as claimed in any one of claims 1-15, further comprising carrier(s) is selected from a group comprising aqueous and/or non-aqueous carrier(s).
  17. 17. A method for preparing the stabilizer composition for preparation of lyophilized viral vaccines as claimed in any one of claims 1-16, comprising mixing: a. one or more sugar(s); b. one or more amino acid(s); c. one or more protein(s) or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s), in the presence of carrier(s) to obtain the stabilizer composition.
  18. 18. A stabilized immunogenic composition comprising the stabilizer composition as claimed in any one of claims 1-16 and one or more live attenuated or inactivated virus.
  19. 19. The stabilized immunogenic composition as claimed in claim 18, wherein the virus(es) is selected from a group comprising Measles, Mumps, Rubella, Varicella Zoster, Polio, Hepatitis, Herpes Simplex 1, Herpes Simplex 2, Parainfluenza Types 1, 2, 3 And 4, Pneumoviruses, Influenza A, Influenza B, Influenza C viruses, Dengue virus, and any part thereof or any combination thereof.
  20. 20. The stabilized immunogenic composition as claimed in claim 19, wherein the virus(es) is selected from a group comprising Measles, Mumps, Rubella, and Varicella zoster, or any combination thereof.

Description

“STABILIZER COMPOSITION FOR IMMUNOGENIC COMPOSITIONS, STABILIZED IMMUNOGENIC COMPOSITIONS, METHODS AND APPLICATIONS THEREOF” TECHNICAL FIELD: [001] The present disclosure relates to the field of immunogenic compositions. More particularly, the present disclosure relates to compositions and methods for stabilizing immunogenic compositions such as vaccines. BACKGROUND OF THE DISCLOSURE: [002] Live attenuated vaccines are amongst the most successful medical interventions in human history. When it comes to viral vaccines, in order for live, attenuated viral vaccines to be effective, they must be capable of replicating after immunization. Thus, any factors that inactivate the virus tends to diminish the potency of vaccine. [003] Live virus vaccines, and particularly attenuated live viruses, are extremely sensitive to the conditions under which they are made and stored. Significant reductions in viral titer are seen during harvest after being cultured, storage and the lyophilization process. Given the significance of viral titer for vaccine effectiveness, stabilizing agents are critical for preserving viral titer to the greatest extent possible. Stabilizing agents are chemical and/or biological substances that can be added to vaccines at various stages of their development to ensure that the vaccine's effectiveness is at its highest when it is used, which can be years after it is prepared. [004] While many stabilizer compositions for viral vaccines have been proposed in the art, many of the live viral immunogenic compositions still require refrigeration, in spite of using stabilizing agents in the compositions. Further, several of the existing stabilizing compositions are complex, requiring several expensive components. Therefore, there is constantly a need to develop novel and economical stabilizing compositions, to improve the stability of live viral vaccine composition. OBJECTS OF THE DISCLOSURE: [005] It is an object of the present disclosure to provide a stabilizer composition for the stabilization of immunogenic compositions. [006] Another object of the present disclosure is to provide a stabilizer composition for stabilizing vaccines. [007] A further object of the present disclosure is to provide a stabilizer composition for stabilizing live attenuated viral vaccines. [008] Particularly, the present disclosure sets out to provide a stabilizer composition for preparation of lyophilized viral vaccines. [009] Another object of the present disclosure is to provide a stabilized immunogenic composition comprising the stabilizer composition of the present invention and at least one live pathogen or antigen. [010] It is an object of the present disclosure to provide a stabilized immunogenic composition comprising the stabilizer composition and at least one live attenuated virus, wherein, the composition preserves desired characteristics of a virus, including the viability, immunogenicity and stability of the virus. [Oil] It is yet another object of the present disclosure to provide a method for preparing the stabilizer composition and the stabilized immunogenic composition as described above. [012] It is a further object of the present disclosure to facilitate application of the stabilized immunogenic composition as described above for immunization of subjects in need thereof. STATEMENT OF THE DISCLOSURE: [013] Addressing the aforesaid need in the art, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines, said composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein(s) or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s). [014] In some embodiments, the sugar(s) in the stabilizer composition is selected from a group comprising monosaccharides, disaccharides, polysaccharides, sugar alcohols and their derivatives or any combination thereof. [015] In some embodiments, the amino acid(s) is a non-acidic amino acid; wherein the amino acid(s) is selected from a group comprising Alanine, Arginine, Asparagine, Cysteine, Glutamine, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine and their salts, any modification or derivative thereof or any combination thereof. [016] Thus, in some embodiments, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines, said composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s), excluding acidic amino acids; c. one or more protein(s) or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s). [017] In some embodiments, the protein(s) and/or peptide(s) is selected from a group comprising hydrolyzed gelatin, lactalbumin, lactalbumin hydrolysate, human serum albumin (HSA), a recombinant human serum albumin (rHSA), and other serum albumins or albumin gene family member or