Search

RU-2026105198-A - Freeze-dried compositions of viral vaccines and a method for their production

RU2026105198ARU 2026105198 ARU2026105198 ARU 2026105198ARU-2026105198-A

Inventors

  • Дхере, Раджив Мхаласакант
  • ГАНГУЛИ, Милан Шоменат
  • ТЬЯГИ, Парикшит Дхарампал
  • САГАР, Умеш Горах
  • НАРАЛЕ, Свапнил Прабхакар
  • АНАСПУРЕ, Яшодхан Дилип
  • ТУПЕ, Шам Рамдас
  • ПУНАВАЛЛА, Сайрус Соли
  • ПУНАВАЛЛА, Адар Сайрус

Assignees

  • СЕРУМ ИНСТИТЬЮТ ОФ ИНДИЯ ПРАЙВИТ ЛИМИТЕД

Dates

Publication Date
20260507
Application Date
20230913
Priority Date
20230801

Claims (20)

  1. 1. A lyophilized or freeze-dried viral vaccine composition containing
  2. a) one or more viral particles or their antigens; and
  3. b) a stabilizer containing one or more sugars or sugar alcohols; one or more amino acids; lactalbumin hydrolysate and gelatin.
  4. 2. The vaccine composition of claim 1, wherein the virus is a flavivirus selected from the group consisting of yellow fever virus, dengue virus, Japanese encephalitis (JE) virus, Kunjin virus, West Nile (WN) virus, tick-borne encephalitis (TBE) virus, St. Louis encephalitis virus, Murray Valley encephalitis virus and Zika virus, a poxvirus selected from the group consisting of orthopoxviruses and avipoxviruses, a morbillivirus or measles virus, mumps virus, rubella virus, an alphavirus selected from the group consisting of Sendai virus, Sindbis virus and Semliki Forest virus (SFV), Ross River virus, encephalitis virus, rhabdovirus or vesicular stomatitis virus (VSV), a retrovirus or RNA tumor virus, an adenovirus selected from the group consisting of adenovirus human adenovirus, bovine adenovirus, canine adenovirus, non-human primate adenovirus, chicken adenovirus, piglet adenovirus and porcine adenovirus, adeno-associated viruses, a lentivirus selected from the group consisting of human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV) and feline immunodeficiency virus (FIV), herpes simplex virus, cytomegalovirus, picornavirus selected from the group consisting of rhinovirus and poliovirus, baculovirus vector or California armyworm multiple nuclear polyhedrosis virus (AcMNPV), hepatitis B virus (HBV), rubulavirus or Newcastle disease virus, parainfluenza virus, influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), respiratory coronavirus (CoV), Ebola virus, Marburg virus, Nipah virus, Chikungunya, rotavirus, human papillomavirus, herpes simplex virus, hepatitis A virus, hepatitis C virus, hepatitis B virus, hepatitis E virus, poliovirus, smallpox virus selected from the group consisting of smallpox virus and monkeypox virus, and varicella-zoster virus antigens; or in which the virus is a live attenuated virus (LAV), an inactivated virus, a chimeric virus, or a recombinant virus.
  5. 3. The vaccine composition of claim 1 or 2, wherein the virus is a live attenuated yellow fever virus present in a 0.5 ml dose of the composition in an amount of at least 3 log 10 IU, or 1000 IU, or 1000 virus particles per 0.5 ml of vaccine;
  6. or in which the yellow fever virus strain is selected from strains 17D, 17D-204, 17D-213 or 17DD;
  7. in which the content of residual impurities originating from eggs or ovalbumin in the composition is in the range of 0.08 to 0.163 μg/0.5 ml of vaccine, the residual moisture content is not more than 3%; and the protein nitrogen content is in the range of 0.09 to 0.22 mg/0.5 ml of vaccine to minimize hypersensitivity/allergic reactions.
  8. 4. The vaccine composition of any one of paragraphs 1-3, wherein the stabilizer comprises one or more sugars or sugar alcohols selected from the group consisting of glucose, sucrose, maltose, lactose, fructose, galactose, mannose, maltulose, isomaltulose, lactulose, mannitol, trehalose, raffinose, lactitol, lactobionic acid, sorbitol, dextrose, fructose, glycerol and fucose, or any combination thereof, present in a concentration of about 1 to 20% (w/v);
  9. or wherein the stabilizer comprises one or more amino acids selected from the group consisting of tricine, leucine, isoleucine, L-histidine, glycine, glutamine, L-arginine, L-arginine hydrochloride, lysine, L-alanine, tryptophan, phenylalanine, tyrosine, valine, cysteine, glycine, histidine, methionine, proline, serine and threonine, or any combination thereof, present in a concentration in the range of about 0.01 to 10% (w/v).
  10. 5. The vaccine composition of any one of claims 1 to 4, wherein the stabilizer comprises a sugar or sugar alcohol that is sorbitol, present at a concentration of about 1 to 20% (w/v);
  11. or the composition comprises a combination of amino acids: tricine at a concentration of about 0.1% to 2% (w/v), L-histidine at a concentration of about 0.1% to 2% (w/v), L-alanine at a concentration of about 0.01% to 1% (w/v) and L-arginine hydrochloride at a concentration of about 0.1% to 5% (w/v); or
  12. the stabilizer includes gelatin in a concentration in the range of approximately 0.1% to 10% (w/v) and lactalbumin hydrolysate in a concentration in the range of approximately 0.05% to 2% (w/v).
  13. 6. A vaccine composition according to any one of claims 1-5, wherein the composition further comprises an adjuvant selected from the group consisting of aluminum hydroxide, aluminum phosphate, aluminum hydroxyphosphate and potassium aluminum sulfate or a mixture thereof;
  14. or the composition further comprises an immunostimulating component selected from the group consisting of an oil and water emulsion, MF-59, liposome, lipopolysaccharide, saponin, lipid A, lipid A derivatives, monophosphoryl lipid A, 3-deacylated monophosphoryl lipid A, AS01, AS03, oligonucleotide, oligonucleotide containing at least one unmethylated CpG and/or liposome, Freund's adjuvant, complete Freund's adjuvant, incomplete Freund's adjuvant, CRL-8300 adjuvant, muramyl dipeptide, TLR-4 agonists, flagellin, flagellins obtained from gram-negative bacteria, TLR-5 agonists, flagellin fragments capable of binding to TLR-5 receptors, QS-21, ISCOMS, Matrix M, dmLT, transferrin binding protein, fflbp, chitosan and saponin in combination with sterols and lipids, or any combination thereof;
  15. or the composition further comprises a pharmaceutically acceptable additive selected from the group consisting of a transporter, an excipient, a binder, a carrier , an isotonic agent, an emulsifier and a humectant, or any combination thereof; wherein the excipient is selected from the group of salts consisting of NaCl, KCl, KH2PO4 , Na2HPO4⋅2H2O , Cal2 and MgCl2 ; a nonionic surfactant selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 85, nonylphenoxypolyethoxyethanol, octylphenoxypolyethoxyethanol, octoxynol 40, nonoxynol-9, triethanolamine, triethanolamine polypeptide oleate, polyoxyethylene-660 hydroxystearate, polyoxyethylene-35 ricinoleate, soy lecithin, alkyl poly(ethylene oxide), poly(ethylene oxide) and poly(propylene oxide) copolymers (EO-PO block copolymers), poly(vinylpyrroloidone), alkyl polyglucosides (such as sucrose monostearate, lauryl diglucoside or sorbitan monolaureate, octyl glucoside and decyl maltoside), fatty alcohols (cetyl alcohol or oleyl alcohol) or cocamides (cocamide ME A, cocamide DEA, cocamide TEA and poloxamer in an amount of 0.001%-0.05%); polymers including dextran, carboxymethylcellulose, hyaluronic acid, cyclodextrin, Pluronic F127, Pluronic F68, Pluronic P123 and EO-PO block copolymers with a molecular weight of more than 3000-4000, or any combination thereof.
  16. 7. A vaccine composition according to any one of claims 1 to 6, wherein the lyophilized or freeze-dried viral vaccine composition is reconstituted with an aqueous solution selected from the group consisting of saline, buffer, and water for injection (WFI), or any combination thereof, prior to its administration or use in vaccination;
  17. or wherein the buffer is selected from the group consisting of sodium chloride, acetate, carbonate, citrate, lactate, gluconate, tartrate, phosphate buffer solution, borate, histidine buffer, succinate buffer, HEPES, TRIS and citrate-phosphate, or any combination thereof;
  18. or wherein the pH of the reconstituted composition is in the range of 6.0 to 7.5; or wherein the reconstituted composition maintains the desired characteristics of bioactivity, efficacy, stability and immunogenicity for at least a period of from about 14 days to about 36 months; and the bioactivity in the reconstituted vaccine composition, expressed on a logarithmic scale (Log 10 IU), or the concentration of the virus is reduced by only about 0.5 log after storage at a temperature of 2-8 °C for 36 months or after storage at a temperature of 25 °C for 6 months or after storage at a temperature of 37 °C for 14 days, compared to the bioactivity of the freshly prepared vaccine composition.
  19. 8. A vaccine composition according to any one of claims 1-7, comprising
  20. a) a live attenuated flavivirus or yellow fever virus present at a dose of not less than 3 log 10 IU per 0.5 ml of the composition, or 1000 IU, or 1000 virus particles;