WO2025004107A1

WO2025004107A1 - Stabilizer composition for immunogenic compositions, stabilized immunogenic compositions, methods and applications thereof

Info

Publication number: WO2025004107A1
Application number: PCT/IN2024/050970
Authority: WO
Inventors: Sivakumar Ayyaswamy PERNAMALLUR; Ramesh Venkat Matur; Harish KANNACHARI; Narender Dev MANTENA; Mahima DATLA
Original assignee: Biological E Limited
Priority date: 2023-06-27
Filing date: 2024-06-27
Publication date: 2025-01-02

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.

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 any combination thereof.

[018] In some embodiments, the mineral salts(s) employable in the stabilizer composition is selected from a group comprising magnesium salts, calcium salts, zinc salts, manganese salts, and the like or any combination thereof.

[019] In some embodiments, the mineral salt(s) is selected from a group comprising zinc sulphate, magnesium sulphate, zinc chloride, and magnesium chloride or any combination thereof. [020] In some embodiments, 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.

[021] In some embodiments, pH of the stabilizer composition is adjusted in accordance with the pathogen or antigen to be stabilized. In some embodiments, the stabilizer composition of the present disclosure may further comprise buffer(s) to maintain the pH. In a non-limiting embodiment, the pH of the stabilizer composition is in the range of about 5 to about 8.

[022] In some embodiments, in addition to each of the above components, the stabilizer composition may further comprise carrier(s). In some embodiments, the carrier(s) is selected from a group comprising aqueous and/or non-aqueous carrier(s).

[023] Also provided in the present disclosure is a method for preparing the stabilizer composition as described above, said method comprising mixing: 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), in the presence of carrier(s) to obtain the stabilizer composition.

[024] Also provided in the present disclosure is a stabilized immunogenic composition comprising the stabilizer composition as described above and one or more live attenuated or inactivated pathogen(s).

[025] In some embodiments, the pathogen(s) is a virus. In some embodiments, 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.

[026] Also provided in the present disclosure is a method for preparing the stabilized immunogenic composition as described above, comprising combining the individual components of the stabilizer composition or the stabilizer composition as described above with the one or more live attenuated or inactivated pathogen(s) in the presence of carrier(s) to obtain the stabilized immunogenic composition.

[027] The present disclosure further provides a kit comprising the stabilized immunogenic composition of the present disclosure, optionally further comprising means for administration of the stabilized immunogenic composition and/or an aqueous solution for reconstituting the stabilized immunogenic composition present in lyophilized form and/or an instruction manual. BRIEF DESCRIPTION OF THE ACCOMPANYING FIGURES

[028] In order that the disclosure may be readily understood and put into practical effect, reference will now be made to exemplary embodiments as illustrated with reference to the accompanying figures. The figures together with detailed description below, are incorporated in and form part of the specification, and serve to further illustrate the embodiments and explain various principles and advantages, where:

[029] Figure 1 depicts the titres of the Measles virus in the stabilized vaccine composition of the present disclosure up to 36 months as observed in long term stability study.

[030] Figure 2 depicts the titres of the Rubella virus in the stabilized vaccine composition of the present disclosure up to 36 months as observed in long term stability study.

DETAILED DESCRIPTION OF THE DISCLOSURE:

[031] Addressing the aforesaid need in the art, the present disclosure is directed towards stabilizer compositions for vaccines, stabilized immunogenic compositions comprising the said composition, method of preparing the stabilizer composition, method of preparing a stabilized immunogenic composition and applications of the stabilizer composition and the stabilized immunogenic compositions. However, before delving into further details of the present disclosure, definitions of some terms/phrases used throughout the present disclosure are provided below.

[032] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the methods belong. Although any vectors, host cells, methods, and compositions similar or equivalent to those described herein can also be used in the practice or testing of the below embodiments, representative embodiments are now described.

Definitions

[033] The phrases ‘stabilizer composition’ and ‘stabilizer composition for preparation of lyophilized viral vaccines’ has been used interchangeably throughout the present disclosure and refer to the stabilized composition as further defined by its components and exclusion(s) therefrom, in the embodiments that follow. [034] As used herein, the term ‘comprising’ when placed before the recitation of steps in a method means that the method encompasses one or more steps that are additional to those expressly recited, and that the additional one or more steps may be performed before, between, and/or after the recited steps. For example, a method comprising steps a, b, and c encompasses a method of steps a, b, x, and c, a method of steps a, b, c, and x, as well as a method of steps x, a, b, and c. Furthermore, the term ‘comprising’ when placed before the recitation of steps in a method does not (although it may) require sequential performance of the listed steps, unless the content clearly dictates otherwise. For example, a method comprising steps a, b, and c encompasses, for example, a method of performing steps in the order of steps a, c, and b, the order of steps c, b, and a, and the order of steps c, a, and b, etc.

[035] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. The suffix ‘ (s)’ at the end of any term in the present disclosure envisages in scope both the singular and plural forms of said term.

[036] As used in this specification and the appended claims, the singular forms ‘a’, ‘an’ and ‘the’ includes both singular and plural references unless the content clearly dictates otherwise. The use of the expression ‘at least’ or ‘at least one’ suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results. As such, the terms ‘a’ (or ‘an’), ‘one or more’, and ‘at least one’ can be used interchangeably herein.

[037] Numerical ranges stated in the form ‘from x to y’ include the values mentioned and those values that he within the range of the respective measurement accuracy as known to the skilled person. If several preferred numerical ranges are stated in this form, of course, all the ranges formed by a combination of the different end points are also included.

[038] The terms ‘about’ or ‘approximately’ as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, are meant to encompass variations of and from the specified value, such as variations of +/- 10% or less, +/-5% or less, +/- 1% or less, and +/-0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier ‘about’ or ‘approximately’ refers is itself also specifically, and preferably, disclosed. [039] As used herein, the terms ‘include’, ‘have’, ‘comprise’, ‘contain’ etc. or any form said terms such as ‘having’, ‘including’, ‘containing’, ‘comprising’ or ‘comprises’ are inclusive and will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[040] As regards the embodiments characterized in this specification, it is intended that each embodiment be read independently as well as in combination with another embodiment. For example, in case of an embodiment 1 reciting 3 alternatives A, B and C, an embodiment 2 reciting 3 alternatives D, E and F and an embodiment 3 reciting 3 alternatives G, H and I, it is to be understood that the specification unambiguously discloses embodiments corresponding to combinations A, D, G; A, D, H; A, D, I; A, E, G; A, E, H; A, E, I; A, F, G; A, F, H; A, F, I; B, D, G; B, D, H; B, D, I; B, E, G; B, E, H; B, E, I; B, F, G; B, F, H; B, F, I; C, D, G; C, D, H; C, D, I; C, E, G; C, E, H; C, E, I; C, F, G; C, F, H; C, F, I, unless specifically mentioned otherwise.

[041] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other embodiments without departing from the scope or spirit of the present methods. Any recited method can be carried out in the order of events recited or in any other order that is logically possible.

Disclosure

[042] The present disclosure relates to vaccine stabilizers, vaccine formulations and specifically, live attenuated vaccines, which show enhanced stability.

[043] More specifically, the present disclosure provides vaccine stabilizers for preparation of lyophilized viral vaccines and viral vaccine formulations comprising the said stabilizer which show enhanced stability.

[044] Accordingly, in order to enable the efficient stabilization of immunogenic compositions, 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).

[045] In some embodiments, the stabilizer composition comprises two or more sugars, with the exclusion of sucrose.

[046] In a non-limiting embodiment, 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.

[047] In some embodiments, the monosaccharide(s) is selected from a group comprising fructose, galactose, glucose, D-mannose, sorbose and their derivatives or any combination thereof.

[048] In some embodiments, the disaccharide(s) is selected from a group comprising lactose, maltose, trehalose, cellobiose and their derivatives or any combination thereof.

[049] In some embodiments, the disaccharide(s) is selected from a group comprising lactose, maltose, trehalose dihydrate and cellobiose or any combination thereof.

[050] In some embodiments, the disaccharide(s) is selected from a group consisting of lactose, maltose, trehalose or trehalose dihydrate and cellobiose or any combination thereof.

[051] In some embodiments, the polysaccharide(s) is selected from a group comprising raffinose, melezitose, maltodextrins, dextrans, starches and their derivatives or any combination thereof.

[052] In some embodiments, the sugar alcohol(s) is selected from a group comprising mannitol, xylitol, maltitol, lactitol, sorbitol, myoinositol and their derivatives or any combination thereof.

[053] In a non-limiting embodiment, the concentration of sugar(s) in the stabilizer composition ranges from about 1 % w/v to about 15 % w/v, including sub-ranges and values therebetween.

[054] In a non-limiting embodiment, the concentration of sugar(s) in the stabilizer composition is about 1 % w/v to about 15 % w/v, about 1 % w/v to about 5 % w/v, about 5 % w/v to about 10 % w/v, about 10 % w/v to about 15 % w/v, about 1 % w/v, about 2 % w/v, about 3 % w/v, about 4 % w/v, about 5 % w/v, about 6 % w/v, about 7 % w/v, about 8 % w/v, about 9 % w/v, about 10 % w/v, about 11 % w/v, about 12 % w/v, about 13 % w/v, about 14 % w/v or about 15 % w/v.

[055] In an exemplary embodiment, the concentration of sugar(s) in the stabilizer composition ranges from about 1 % w/v to about 10 % w/v.

[056] In an exemplary non-limiting embodiment, the sugar(s) in the stabilizer composition is a combination of sorbitol and trehalose. [057] In another exemplary non-limiting embodiment, the sugar(s) in the stabilizer composition is a combination of sorbitol and trehalose dihydrate.

[058] In some embodiments, the concentration of sorbitol in the stabilizer composition is in the range of about 1 % w/v to about 10 % w/v. In some embodiments, the concentration of sorbitol in the stabilizer composition is in the range of about 3 % w/v to about 7 % w/v. In another embodiment, the concentration of trehalose in the stabilizer composition is in the range of about 1 % w/v to about 10 % w/v. In some embodiments, the concentration of trehalose in the stabilizer composition is in the range of about 3% w/v to about 7% w/v. In some embodiments, the concentration of trehalose dihydrate in the stabilizer composition is in the range of about 3 % w/v to about 7% w/v.

[059] In an exemplary embodiment, the concentration of trehalose or trehalose dihydrate in the stabilizer composition is in the range of about 3% w/v to about 7% w/v and the concentration of sorbitol in the stabilizer composition is in the range of about 3 % w/v to about 7 % w/v.

[060] In a non-limiting embodiment, the stabilizer composition is substantially free of sucrose. [061] In some embodiments, the stabilizer composition comprises two or more amino acids.

[062] In some embodiments, the stabilizer composition comprises three or more amino acids.

[063] In some embodiments, the stabilizer composition comprises four or more amino acids.

[064] In some embodiments, the stabilizer composition comprises five or more amino acids.

[065] In a preferred embodiment, the amino acid(s) is a non-acidic amino acid(s).

[066] In some embodiments, 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.

[067] In some embodiments, 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.

[068] Accordingly, in some embodiments, the stabilizer composition for preparation of lyophilized viral vaccines comprises: 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).

[069] In some embodiments, the amino acid(s) is selected from a group consisting of 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.

[070] In a non-limiting exemplary embodiment, the amino acid(s) is selected from a group comprising Alanine, Arginine, Glycine, Histidine and Proline, their salts, any modification or derivative thereof or any combination thereof.

[071] In another non-limiting exemplary embodiment, the amino acid(s) is selected from a group comprising Alanine, Arginine monohydrochloride, Glycine, Histidine, Proline, their salts, any modification or derivative thereof or any combination thereof.

[072] In another non-limiting exemplary embodiment, the amino acids are Alanine, Arginine/ Arginine monohydrochloride, Glycine, Histidine and Proline.

[073] In a non-limiting exemplary embodiment, the amino acids are Glycine and Proline, their salts, any modification or derivative thereof.

[074] In another non-limiting exemplary embodiment, the amino acids are Glycine and Proline. [075] In some embodiments, the concentration of amino acid(s) in the stabilizer composition ranges from about 0.01 % w/v to about 10 % w/v, including sub-ranges or values therebetween.

[076] In a non-limiting embodiment, the concentration of amino acid(s) in the stabilizer composition is about 0.01 %w/v to 2 %w/v, about 2 % w/v to about 4 % w/v, about 4 % w/v to about 6 % w/v, about 6 % w/v to about 8 % w/v, about 8 % w/v to about 10% w/v, about 0.01% w/v, about 0.1 % w/v, about 1 % w/v, about 2 % w/v, about 3 % w/v, about 4 % w/v, about 5 % w/v, about 6 % w/v, about 7 % w/v, about 8 % w/v, about 9 % w/v or about 10 % w/v.

[077] In some embodiments, the stabilizer composition comprises amino acid alanine at a concentration in the range of about 0.01% w/v to about 5% w/v. In some non-limiting embodiments, the stabilizer composition comprises amino acid alanine at a concentration in the range of about 0.05% w/v to about 2% w/v. [078] In some embodiments, the stabilizer composition comprises amino acid arginine or arginine monohydrochloride at a concentration in the range of about 0.01 % w/v to about 5 % w/v. In some non-limiting embodiments, the stabilizer composition comprises amino acid arginine or arginine monohydrochloride at a concentration in the range of about 0.05% w/v to about 2% w/v. [079] In some embodiments, the stabilizer composition comprises amino acid glycine at a concentration ranging from about 0.1 % w/v to about 5 % w/v. In some non-limiting embodiments, the stabilizer composition comprises amino acid glycine at a concentration in the range of about 0.5% w/v to about 3% w/v.

[080] In some embodiments, the stabilizer composition comprises amino acid histidine at a concentration ranging from about 0.01 % w/v to about 5 % w/v. In some non-limiting embodiments, the stabilizer composition comprises amino acid histidine at a concentration in the range of about 0.05% w/v to about 2% w/v.

[081] In some embodiments, the stabilizer composition comprises amino acid proline at a concentration ranging from about 0.1 % w/v to about 5 % w/v. In some non-limiting embodiments, the stabilizer composition comprises amino acid proline at a concentration in the range of about 0.5% w/v to about 3% w/v.

[082] In some embodiments, the stabilizer composition comprises amino acids proline and glycine, wherein glycine and proline are each present at a concentration in the range of about 0.1 % w/v to about 5 % w/v, preferably in the range of about 0.5% w/v to about 3% w/v. In some embodiments, the stabilizer composition further comprises one or more amino acids selected from the 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.

[083] Thus, in some embodiments, the amino acid(s) is selected from a group comprising alanine, arginine/arginine monohydrochloride, glycine, histidine and proline, or any combination thereof; wherein alanine, arginine or arginine monohydrochloride and histidine are each present at a concentration in the range of about 0.01% w/v to about 5% w/v; and wherein glycine and proline are each present at a concentration in the range of about 0.1 % w/v to about 5 % w/v.

[084] In some embodiments, the stabilizer composition comprises one or more protein(s) and/or peptide(s). [085] In some embodiments, the stabilizer composition comprises two or more protein(s) and/or peptide(s).

[086] In a non-limiting embodiment, protein(s) and/or peptide(s) employable in the stabilizer composition 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.

[087] In a non-limiting exemplary embodiment, the protein or peptide is hydrolyzed gelatin and/or human serum albumin (HSA).

[088] non-limiting exemplary embodiment, the protein or peptide is hydrolyzed gelatin and human serum albumin (HSA).

[089] In some embodiments, the concentration of protein or peptides in the stabilizer composition ranges from about 0.05% w/v to about 10% w/v, including sub-ranges or values therebetween.

[090] In some embodiments, the concentration of protein or peptides in the stabilizer composition ranges from about 0.5% w/v to about 10% w/v, including sub-ranges or values therebetween.

[091] In a non-limiting embodiment, the concentration of protein or peptides in the stabilizer composition is about 0.05% w/v to about 0.5 w/v, 0.5% w/v to about 2% w/v, about 2% w/v to about 4% w/v, about 4% w/v to about 6% w/v, about 6% w/v to about 8% w/v or about 8% w/v to about 10% w/v, about 0.5% w/v, about 1% w/v, about 2% w/v, about 3% w/v, about 4% w/v, about 5% w/v, about 6% w/v, about 7% w/v, about 8% w/v, about 9% w/v or about 10% w/v.

[092] In some embodiments, the stabilizer composition comprises hydrolyzed gelatin at a concentration ranging from about 1% w/v to about 10% w/v. In some non-limiting embodiments, the stabilizer composition comprises hydrolyzed gelatin at a concentration ranging from about 3% w/v to about 6% w/v.

[093] In some embodiments, the stabilizer composition comprises HSA at a concentration ranging from about 0.05 %w/v to about 2 % w/v. In some non-limiting embodiments, the stabilizer composition comprises HSA at a concentration ranging from about 0.05% w/v to about 1% w/v. [094] In some embodiments, the stabilizer composition comprises one or more mineral salt(s).

[095] In a non-limiting embodiment, the mineral salts(s) employable in the stabilizer composition is selected from a group comprising magnesium salts, calcium salts, zinc salts, manganese salts, and the like or any combination thereof. [096] In some non-limiting embodiments, the mineral salts are selected from a group comprising chlorides, sulphates, and nitrates or any combination thereof.

[097] In some embodiments, the concentration of mineral salt(s) in the stabilizer composition ranges from about 0.1 % w/v to about 10% w/v, including sub-ranges or values therebetween.

[098] In a non-limiting embodiment, the concentration of mineral salt(s) in the stabilizer composition is about 0.1 % w/v to about 0.5% w/v, about 0.5% w/v to about 2% w/v, about 2% w/v to about 4% w/v, about 4% w/v to about 6% w/v, about 6% w/v to about 8% w/v or about 8% w/v to about 10% w/v, about 0.1 w/v, about 0.5% w/v, about 1% w/v, about 2% w/v, about 3% w/v, about 4% w/v, about 5% w/v, about 6% w/v, about 7% w/v, about 8% w/v, about 9% w/v or about 10% w/v.

[099] In a non-limiting exemplary embodiment, the mineral salt is selected from zinc sulphate, magnesium sulphate, zinc chloride, and magnesium chloride. In a preferred embodiment, the mineral salt is magnesium sulphate heptahydrate. In some embodiments, concentration of said mineral salt in the stabilizer composition ranges from about 0.1 % w/v to about 10 % w/v.

[0100] In another non-limiting embodiment, the mineral salt is magnesium sulphate heptahydrate, wherein the concentration of Magnesium Sulphate heptahydrate in the stabilizer composition ranges from about 0.5 % w/v to about 5% w/v. In another non-limiting embodiment, the concentration of Magnesium Sulphate heptahydrate in the stabilizer composition ranges from about 0.5 % w/v to about 2% w/v.

[0101] In some embodiments, pH of the stabilizer composition is adjusted in accordance with the pathogen or antigen to be stabilized.

[0102] In a non-limiting embodiment, pH of the stabilizer composition is in the range of about 5 to about 8, including sub-ranges or values therebetween, such as about 5 to 7, about 5 to 6, about 6 to 8, about 6 to 7, about 5.5 to 7.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, or about 8.

[0103] In a non-limiting exemplary embodiment, the pH of the stabilizer composition is in the range of about 5.5 to about 7.5.

[0104] The stabilizer composition of the present disclosure may further comprise buffer(s) to maintain the pH.

[0105] In a non-limiting embodiment, the buffer(s) is selected from a group comprising phosphate buffers such as phosphate buffered saline (PBS), acetate buffers, benzoate buffer, phosphate 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.

[0106] In a non-limiting exemplary embodiment, the buffer is a phosphate - citrate buffer that ensures buffering across the preferred pH range. In some embodiments, 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.

[0107] In a non-limiting embodiment, the buffer is prepared by dissolving disodium hydrogen phosphate and citric acid in water, wherein the concentration of disodium hydrogen phosphate ranges from about 5 mM to about 15 mM and the concentration of citric acid ranges from about 0.5 mM to about 5 mM.

[0108] In some embodiments, the buffer comprises disodium hydrogen phosphate and citric acid dissolved in water, wherein the concentration of disodium hydrogen phosphate is in the range of about 10 mM to about 15 mM and the concentration of citric acid is in the range of about 0.5 mM to about 2.5 mM.

[0109] Accordingly, in some exemplary embodiments, in the stabilizer composition of the present disclosure, 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 0.5% w/v to about 10% w/v; the mineral salt(s) is present at a concentration of about 0.1 % w/v to about 10% w/v; and/or a a phosphate - citrate buffer wherein the phosphate is present in a concentration range of about 5 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 5 mM.

[0110] In some non-limiting embodiments, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines comprising: a. hydrolyzed gelatin; b. HSA; c. sorbitol; d. trehalose dihyhrate; e. phosphate-citrate buffer; f. histidine; g. alanine; h. arginine monohydrochloride; i. proline; j. glycine; and k. magnesium sulphate heptahydrate.

[0111] In some embodiments, the stabilizer composition of the present disclosure comprises: a. About 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. About 0.05 %w/v to about 2 % w/v HS A; c. About 1 % w/v to about 10 % w/v sorbitol; d. About 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 5 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 5 mM; f. About 0.01 % w/v to about 5 % w/v histidine; g. About 0.01% w/v to about 5% w/v alanine; h. About 0.01% w/v to about 5% w/v arginine monohydrochloride; i. About 0.1 % w/v to about 5 % w/v proline; j. About 0.1 % w/v to about 5 % w/v glycine; and k. About 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate.

[0112] In a non-limiting embodiment, the stabilizer composition of the present disclosure comprises: a. About 3 % w/v to about 6% w/v hydrolyzed gelatin; b. About 0.05 % w/v to about 1 % w/v HSA; c. About 3 % w/v to about 7 % w/v sorbitol; d. About 3 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 10 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 2.5 mM; f. About 0.05% w/v to about 2% w/v histidine; g. About 0.05% w/v to about 2% w/v alanine; h. About 0.05% w/v to about 2% w/v arginine monohydrochloride; i. About 0.5% w/v to about 3% w/v proline; j. About 0.5% w/v to about 3% w/v glycine; and k. About 0.5 % w/v to about 2% w/v magnesium sulphate heptahydrate.

[0113] In some exemplary embodiments, the stabilizer composition for preparation of lyophilized viral vaccines comprises: a. hydrolyzed gelatin; b. HSA; c. sorbitol; d. trehalose dihyhrate; e. phosphate-citrate buffer; f. proline; g. glycine; and h. magnesium sulphate heptahydrate.

[0114] In some exemplary embodiments, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines comprising: a. About 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. About 0.05 %w/v to about 2 % w/v HSA; c. About 1 % w/v to about 10 % w/v sorbitol; d. About 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 5 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 5 mM, f. About 0.1 % w/v to about 5 % w/v proline; g. About 0.1 % w/v to about 5 % w/v glycine; and h. About 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate.

[0115] In a non-limiting embodiment, the stabilizer composition for preparation of lyophilized viral vaccines comprises: a. About 3 % w/v to about 6% w/v hydrolyzed gelatin; b. About 0.05 % w/v to about 1 % w/v HSA; c. About 3 % w/v to about 7 % w/v sorbitol; d. About 3 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 10 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 2.5 mM; f. About 0.5% w/v to about 3% w/v proline; g. About 0.5% w/v to about 3% w/v glycine; and h. About 0.5 % w/v to about 2% w/v magnesium sulphate heptahydrate.

[0116] In some embodiments, in addition to each of the above components, the stabilizer composition may further comprise carrier(s). Without intending to be limited by theory, the carrier allows dissolution of the components of the stabilizer composition and/or stable interaction of the stabilizer composition and the pathogen and/or antigen during preparation of the stabilized immunogenic composition comprising the stabilizer composition.

[0117] In some embodiments, the carrier(s) is selected from a group comprising aqueous and/or non-aqueous carriers.

[0118] In a non-limiting embodiment, the carrier(s) is selected from a group comprising water, ethanol, glycerol, alcoholic/aqueous solutions, emulsions, suspensions, saline and buffered media or any combination thereof. In a non-limiting exemplary embodiment, the carrier is water.

[0119] In a non-limiting embodiment, the stabilizer composition finds application in preparation of stabilized immunogenic compositions. Such compositions may be lyophilized for storage. The carrier(s) may thus be removed during lyophilization.

[0120] Further provided in the present disclosure is a stabilized immunogenic composition comprising the stabilizer composition as described above and one or more immunogen(s).

[0121] In an exemplary embodiment, the immunogen(s) is selected from antigen(s) and pathogen(s) or any part thereof.

[0122] In some embodiments, the pathogen(s) is selected from a group comprising inactivated pathogen(s) and live attenuated pathogen(s) or a combination thereof.

[0123] In some embodiments, the pathogen(s) is a live attenuated pathogen(s).

[0124] Accordingly, in an exemplary embodiment, provided in the present disclosure is a stabilized immunogenic composition comprising the stabilizer composition as described above and one or more live attenuated or inactivated pathogen(s).

[0125] In a non-limiting exemplary embodiment, the live attenuated or inactivated pathogen(s) is a live attenuated or inactivated virus. [0126] In some embodiments, provided in the present disclosure is a stabilized immunogenic composition comprising the stabilizer composition as described above and one or more live attenuated or inactivated virus(s). In some embodiments, the stabilized immunogenic composition comprises two or more strains of live attenuated or inactivated virus.

[0127] In some embodiments, the live attenuated or inactivated virus is selected from a group comprising viruses from family myoviridae, siphoviridae, podoviridae, tectiviridae, corticoviridae, plasmaviridae, lipothrixviridae, fuselloviridae, poxviridae, iridoviridae, phycodnaviridae, baculoviridae, herpesviridae, adenoviridae, papovaviridae, polydnaviridae, inoviridae, microviridae, geminiviridae, circoviridae, parvoviridae, hepadnaviridae, retroviridae, cystoviridae, reoviridae, birnaviridae, paramyxoviridae, rhabdoviridae, Filoviridae, orthomyxoviridae, bunyaviridae, arenaviridae, leviviridae, picornaviridae, sequiviridae, comoviridae, potyviridae, caliciviridae, astroviridae, nodaviridae, tetraviridae, tombusviridae, coronaviridae, flaviviridae, togaviridae, barnaviridae, and bornaviridae or any combination thereof.

[0128] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure may comprise of virus from one, two, three, four, five, six, seven, eight, nine, ten or more families.

[0129] In some embodiments, the stabilized immunogenic composition of the present disclosure is a monovalent or a multivalent immunogenic composition, depending on the number of different pathogens or antigens against which the stabilized immunogenic composition of the present disclosure is capable of eliciting a neutralizing antibody response. In a non-limiting embodiment, the multivalent immunogenic composition of the present disclosure is capable of eliciting response against two, three, four, five or six or more different viral pathogens.

[0130] In some embodiments, the stabilized immunogenic composition of the present disclosure comprises virus(es) 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.

[0131] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure is a monovalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Measles virus. [0132] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure is a monovalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Mumps virus.

[0133] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure is a monovalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Rubella virus.

[0134] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure is a tetravalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Measles, Mumps, Rubella and Varicella zoster virus. Thus, in some embodiments, the stabilized immunogenic composition of the present disclosure comprises live attenuated Measles, Mumps, Rubella and Varicella zoster virus.

[0135] In a non-limiting embodiment, the stabilized immunogenic composition of the present disclosure is a trivalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Measles, Mumps and Rubella virus. Thus, in some embodiments, the stabilized immunogenic composition of the present disclosure comprises live attenuated Measles, Mumps and Rubella virus.

[0136] In a non-limiting exemplary embodiment, the stabilized immunogenic composition of the present disclosure is a bivalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Measles and Rubella virus. Thus, in some embodiments, the stabilized immunogenic composition of the present disclosure comprises live attenuated Measles and Rubella virus.

[0137] In some exemplary embodiments, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines, comprising one or more virus(es) selected from a group comprising Measles, Mumps, Rubella and Varicella virus, wherein the stabilizer composition comprises: a. about 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. about 0.05 %w/v to about 2 % w/v HSA; c. about 1 % w/v to about 10 % w/v sorbitol; d. about 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein phosphate is present in a concentration range of about 5 mM to about 15 mM and citrate is present in a concentration range of about 0.5 mM to about 5 mM, f. about 0.1 % w/v to about 5 % w/v proline; g. about 0.1 % w/v to about 5 % w/v glycine; and h. about 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate.

[0138] In some exemplary embodiments, the present disclosure provides a stabilizer composition for preparation of lyophilized viral vaccines, comprising one or more virus(es) selected from a group comprising Measles, Mumps, and Rubella virus, wherein the stabilizer composition comprises: a. about 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. about 0.05 %w/v to about 2 % w/v HSA; c. about 1 % w/v to about 10 % w/v sorbitol; d. about 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein phosphate is present in a concentration range of about 5 mM to about 15 mM and citrate is present in a concentration range of about 0.5 mM to about 5 mM. f. about 0.1 % w/v to about 5 % w/v proline; g. about 0.1 % w/v to about 5 % w/v glycine; and

[0139] about 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate

[0140] In a non-limiting embodiment, the stabilizer composition for preparation of lyophilized viral vaccines, comprising one or more virus(es) selected from a group comprising Measles, Mumps, Rubella and Varicella virus, wherein the stabilizer composition comprises: a. about 3 % w/v to about 6% w/v hydrolyzed gelatin; b. about 0.05 % w/v to about 1 % w/v HSA; c. about 3 % w/v to about 7 % w/v sorbitol; d. about 3 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 10 mM to about 15 mM and citrate is present in a concentration range of about 0.5 mM to about 2.5 mM; f. about 0.5% w/v to about 3% w/v proline; g. about 0.5% w/v to about 3% w/v glycine; and h. about 0.5 % w/v to about 2% w/v magnesium sulphate heptahydrate.

[0141] Accordingly, in some embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Measles virus, a live attenuated Mumps virus, a live attenuated Rubella virus and/or a live attenuated Varicella virus, and a stabilizer composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0142] Accordingly, in some embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Measles virus, a live attenuated Mumps virus and/or a live attenuated Rubella virus and a stabilizer composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0143] In some embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Measles virus, a live attenuated Mumps virus and/or a live attenuated Rubella virus and a stabilizer composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s), wherein the stabilizer composition is specifically intended for preparation of lyophilized viral vaccines. [0144] In some embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Measles virus, a live attenuated Mumps virus and/or a live attenuated Rubella virus and a stabilizer 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 or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s), wherein the stabilizer composition is specifically intended for preparation of lyophilized viral vaccines.

[0145] In some embodiments, the stabilized immunogenic composition of the present disclosure comprises live attenuated Measles and Rubella virus.

[0146] Accordingly, in some embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Measles virus, a live attenuated Rubella virus and a stabilizer composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0147] In some embodiments, the stabilized immunogenic composition comprises a live attenuated Measles virus, a live attenuated Rubella virus and a stabilizer 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 or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0148] In some embodiments, the Measles virus strain is selected from a group comprising AIK- C, Schwarz, Moraten, CAM70, TD97, Leningrad- 16, Shanghai- 191, Edmonston Zagreb, a recombinant or a genetically modified form of any of these virus strains, or any combination thereof. [0149] In an exemplary embodiment, the Measles virus vaccine strain is Edmonston Zagreb strain. [0150] In a non-limiting embodiment, the Rubella virus strain is selected from a group comprising Matsuba, DCRB19, Takahashi, Matsuura, TO-336, RA 27/3 Wistar, a recombinant or a genetically modified form of any of these virus strains, or any combination thereof.

[0151] In an exemplary embodiment, the Rubella virus strain is RA 27/3 Wistar strain.

[0152] In some embodiments, the stabilized immunogenic composition of the present disclosure is a bivalent immunogenic composition, capable of eliciting a neutralizing antibody titer against Measles and Rubella virus.

[0153] In a non-limiting exemplary embodiment, the bivalent stabilized immunogenic composition of the present disclosure comprises live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus.

[0154] Accordingly, in a non-limiting exemplary embodiment, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0155] In another non-limiting embodiment, the stabilized immunogenic composition comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer 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 or peptide(s); d. one or more mineral salt(s); and e. one or more buffer(s).

[0156] In some embodiments, the stabilized immunogenic composition comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. hydrolyzed gelatin; b. HSA; c. sorbitol; d. trehalose dihyhrate; e. phosphate-citrate buffer; f. histidine; g. alanine; h. arginine monohydrochloride; i. proline; j. glycine; and k. magnesium sulphate heptahydrate.

[0157] In a non-limiting embodiment, the stabilized immunogenic composition comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. About 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. About 0.05 %w/v to about 2 % w/v HSA; c. About 1 % w/v to about 10 % w/v sorbitol; d. About 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 5 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 5 mM; f. About 0.01 % w/v to about 5 % w/v histidine; g. About 0.01% w/v to about 5% w/v alanine; h. About 0.01% w/v to about 5% w/v arginine monohydrochloride; i. About 0.1 % w/v to about 5 % w/v proline; j. About 0.1 % w/v to about 5 % w/v glycine; and k. About 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate.

[0158] In another non-limiting embodiment, the stabilized immunogenic composition comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. About 3 % w/v to about 6% w/v hydrolyzed gelatin; b. About 0.05 % w/v to about 1 % w/v HSA; c. About 3 % w/v to about 7 % w/v sorbitol; d. About 3 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 10 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 2.5 mM; f. About 0.05% w/v to about 2% w/v histidine; g. About 0.05% w/v to about 2% w/v alanine; h. About 0.05% w/v to about 2% w/v arginine monohydrochloride; i. About 0.5% w/v to about 3% w/v proline; j. About 0.5% w/v to about 3% w/v glycine; and k. About 0.5 % w/v to about 2% w/v magnesium sulphate heptahydrate.

[0159] In some embodiments, the stabilized immunogenic composition of the present disclosure comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. hydrolyzed gelatin; b. HSA; c. sorbitol; d. trehalose dihyhrate; e. phosphate-citrate buffer; f. proline; g. glycine; and h. magnesium sulphate heptahydrate.

[0160] In some embodiments, the stabilized immunogenic composition comprises a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. About 1 % w/v to about 10 % w/v hydrolyzed gelatin; b. About 0.05 %w/v to about 2 % w/v HSA; c. About 1 % w/v to about 10 % w/v sorbitol; d. About 2 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein phosphate is present in a concentration range of about 5 mM to about 15 mM and citrate is present in a concentration range of about 0.5 mM to about 5 mM; f. About 0.1 % w/v to about 5 % w/v proline; g. About 0.1 % w/v to about 5 % w/v glycine; and h. About 0.1 % w/v to about 10 % w/v magnesium sulphate heptahydrate.

[0161] In some exemplary non-limiting embodiments, the present disclosure provides a stabilized immunogenic composition comprising a live attenuated Edmonston Zagreb strain of the Measles virus and live attenuated RA 27/3 Wistar strain of the Rubella virus and a stabilizer composition comprising: a. About 3 % w/v to about 6% w/v hydrolyzed gelatin; b. About 0.05 % w/v to about 1 % w/v HSA; c. About 3 % w/v to about 7 % w/v sorbitol; d. About 3 % w/v to about 7 % w/v trehalose dihyhrate; e. phosphate-citrate buffer wherein the phosphate is present in a concentration range of about 10 mM to about 15 mM and the citrate is present in a concentration range of about 0.5 mM to about 2.5 mM; f. About 0.5% w/v to about 3% w/v proline; g. About 0.5% w/v to about 3% w/v glycine; and h. About 0.5 % w/v to about 2% w/v magnesium sulphate heptahydrate.

[0162] In some embodiments, said bivalent immunogenic composition comprises live attenuated Measles virus particles in the range of 3.0 Log CCID50/dose to 6.0 Log CCID50/dose and live attenuated Rubella virus particles in the range of 3.0 Log CCID50/dose to 6.0 Log CCID50/dose. [0163] In some embodiments, the stabilized immunogenic composition of the present disclosure is amenable to lyophilization. The stabilized immunogenic composition of the present disclosure may thus be lyophilized to obtain a lyophilized stabilized immunogenic composition. Accordingly, in some embodiments, the stabilized immunogenic composition comprising the stabilizer composition of the present disclosure and immunogen of choice is a lyophilized immunogenic composition. In a non-limiting embodiment, the carrier(s) that is part of the stabilizer composition is removed in view of the lyophilization and therefore does not form part of the stabilized immunogenic composition. [0164] The lyophilized stabilized immunogenic composition of the present disclosure shows remarkable thermal stability, with extremely low loss in infectivity, when stored at a wide range of temperatures. The lyophilized stabilized immunogenic composition described herein may thus be used to preserve and stabilize antigen or pathogen for an extended period of time. In a nonlimiting embodiment, the lyophilized stabilized immunogenic composition, prepared as per the present disclosure, may be stored for up to thirty-six months at a temperature of about 2°C to about 8°C without losing potency.

[0165] The lyophilized stabilized immunogenic composition of the present disclosure shows an intact physical appearance, with a uniform cake appearance.

[0166] In a non-limiting embodiment, the lyophilized stabilized immunogenic composition may be reconstituted with an aqueous solution selected from saline or water for injection (WFI), to obtain a stabilized immunogenic composition.

[0167] In some embodiments, the lyophilized stabilized immunogenic composition of the present disclosure is a vaccine.

[0168] In a non-limiting exemplary embodiment, the lyophilized stabilized immunogenic composition of the present disclosure is a Measles, Mumps and/or Rubella vaccine.

[0169] In another non-limiting exemplary embodiment, the lyophilized stabilized immunogenic composition of the present disclosure is a Measles and Rubella vaccine.

[0170] In yet another non-limiting exemplary embodiment, the lyophilized stabilized immunogenic composition of the present disclosure is a Measles, Mumps and Rubella vaccine.

[0171] The WHO thermal stability criteria requires that in the freeze-dried state, Measles, Mumps, and / or Rubella vaccine must retain a minimum potency of at least 3.0 log CCID50 live virus particles per human dose after exposure to a temperature of 37 °C for at least one week. Further, the virus titer should not decrease by more than 1.0 log CCID50 during incubation. In some embodiments, the lyophilized stabilized vaccine composition of the present disclosure satisfies the said test criteria. In some embodiments, the decrease in viral titer of the stabilized lyophilized MMR vaccine of the present disclosure, when stored at about 37 °C for a time period of about 7 days, is much less than 1.0 log CCID50 level set by the test criteria. In some embodiments, the decrease in viral titer is much less than 1.0 log CCID 50, even when the stabilized lyophilized MMR vaccine of the present disclosure is stored at about 37 °C for a time period of about 14 days or more, such as, but not limiting to about 21 days, which is much beyond the WHO criteria for thermal stability.

[0172] Thus, in some embodiments, the present disclosure provides a stabilized vaccine wherein the vaccine is essentially constituted of a suspension of immunogen(s) such as but not limited to pathogen(s) or antigen(s) of interest in the stabilizer composition described in the above embodiments. In some embodiments, the stabilized vaccine is a live attenuated vaccine. In some embodiments, the said vaccine is in lyophilized form.

[0173] Further provided in the present disclosure is a method for preparing the stabilizer composition as described above.

[0174] Although the subsequent embodiments focus on a method of preparing the said composition, the features and characteristics of the stabilizer composition, including the components and their concentrations as such are as described by any of the embodiments above. For the sake of brevity, and avoiding repetition, each of those embodiments are not being reiterated here again with respect to the method. However, each of the said embodiments completely fall within the purview of the method described herein.

[0175] In some embodiments, further provided in the present disclosure is a method for preparing the stabilizer composition as described above, said method comprising mixing: 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), in the presence of carrier(s) to obtain the stabilizer composition.

[0176] In some embodiments, the method for preparing the stabilizer composition as described above comprises: 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), in the presence of carrier(s) to obtain the stabilizer composition. [0177] In some embodiments, the aforesaid method is not restricted by the order of mixing/combining of components. In some embodiments, the components are contacted with each other sequentially and combined/mixed to form the composition, with no restriction on the order of contacting the respective components. In some embodiments, all components are contacted simultaneously and mixed/combined to obtain the stabilizer composition as described above.

[0178] As mentioned above, the stabilizer composition of the present disclosure finds application in preparation of stabilized immunogenic compositions. Such compositions may be lyophilized for storage. The carrier may thus be removed during lyophilization of the stabilized immunogenic compositions.

[0179] In some embodiments, the present disclosure further provides a method for preparing the stabilized immunogenic composition as described above.

[0180] In some embodiments, the said method comprises combining the stabilizer composition of the present disclosure with suitable immunogen(s).

[0181] In some embodiments, the method for preparing the stabilized immunogenic composition comprises combining the stabilizer composition of the present disclosure with suitable antigen(s) or pathog en(s). In some embodiments, the stabilizer composition is pre-prepared and combined with suitable antigen(s) or pathogen(s) to obtain the stabilized immunogenic composition. In some embodiments, the components of the stabilizer composition are individually mixed with the suitable antigen(s) or pathogen(s) either simultaneously or sequentially, in any order, to obtain the stabilized immunogenic composition.

[0182] Thus, in some embodiments, the said method comprises combining immunogen(s) such as but not limited to suitable antigen(s) or pathogen(s) with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein 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 stabilized immunogenic composition.

[0183] In some embodiments, the said method comprises combining immunogen(s) such as but not limited to suitable antigen(s) or pathogen(s) with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s), excluding acidic amino acids; c. one or more protein 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 stabilized immunogenic composition.

[0184] In a non-limiting exemplary embodiment, the said method comprises combining live attenuated Measles virus, live attenuated Mumps virus and/or live attenuated Rubella virus with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein 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 stabilized immunogenic composition.

[0185] In another non-limiting exemplary embodiment, the method for preparing the stabilized immunogenic composition comprises combining the live attenuated Measles virus, live attenuated Mumps virus and live attenuated Rubella virus, with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein 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 stabilized immunogenic composition.

[0186] In yet another non-limiting exemplary embodiment, the method for preparing the stabilized immunogenic composition comprises combining live attenuated Measles virus and/or live attenuated Rubella virus, with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s); c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. a buffer in the presence of carrier(s) to obtain the stabilized immunogenic composition. [0187] In a further non-limiting exemplary embodiment, the method for preparing the stabilized immunogenic composition comprises combining live attenuated Measles virus and/or live attenuated Rubella virus, with: a. one or more sugar(s), excluding sucrose; b. one or more amino acid(s), excluding acidic amino acids; c. one or more protein or peptide(s); d. one or more mineral salt(s); and e. a buffer in the presence of carrier(s) to obtain the stabilized immunogenic composition.

[0188] In an embodiment, the method for preparing the stabilized immunogenic composition further comprises lyophilization.

[0189] In some embodiments, the aforesaid method is not restricted by the order of mixing/combining of components. In some embodiments, the components are contacted with each other sequentially and combined/mixed to form the stabilized immunogenic composition, with no restriction on the order of contacting the respective components. In some embodiments, all components are contacted simultaneously and mixed/combined to obtain the stabilized immunogenic composition as described above. In some embodiments, the stabilizer composition is pre-prepared and mixed with the pathogen and/or antigen to obtain the stabilized immunogenic composition.

[0190] In some embodiments, the stabilized immunogenic composition is further subjected to lyophilization to obtain a lyophilized stabilized immunogenic composition.

[0191] Lyophilization may be performed utilizing methods and tools that are known in the art. Without intending to be limited by theory, lyophilization involves first freezing and then one or more drying stages.

[0192] In some embodiments, the stabilized immunogenic composition is subjected to lyophilization in a lyophilizer. In a non-limiting embodiment, the stabilized immunogenic composition is placed into the lyophilizer, and shelves of the lyophilizer are then chilled to a target set temperature at a controlled rate. The product is maintained at the freezing stage for a predetermined amount of time.

[0193] In the freezing stage, the stabilized immunogenic composition may be cooled, for a predetermined period of time, to a temperature lower than about 0°C to form a frozen stabilized immunogenic composition. In some embodiments, the liquid stabilized immunogenic composition may be cooled to a temperature of about -40°C or lower. In some embodiments, the liquid stabilized immunogenic composition may be cooled for a time period ranging from about 2 hours to about 10 hours.

[0194] The frozen stabilized immunogenic composition may then be dried under reduced pressure (e.g., by applying a vacuum) to obtain the lyophilized stabilized immunogenic composition. In some embodiments, a vacuum pressure ranging from about 25 pbar to about 250 pbar may be applied to the frozen stabilized immunogenic composition at the drying step. In yet another embodiment, the drying step may be performed at a temperature ranging from about -40°C to about +30°C. Optionally, the drying step may also be performed in one or more stages.

[0195] As mentioned above, the said step of lyophilization may lead to removal of the carrier(s) from the stabilized immunogenic composition.

[0196] In some embodiments, the present disclosure envisages a method of stabilizing an immunogenic composition comprising mixing the stabilizer composition as described above with suitable immunogen(s) such as but not limited to antigen(s) or pathogen(s). In some embodiments, the method further comprises lyophilizing the aforesaid immunogenic composition to obtain a lyophilized stabilized immunogenic composition.

[0197] In a non-limiting embodiment, the lyophilized stabilized immunogenic composition may be reconstituted with an aqueous solution selected from saline or WFI (water for injection), to obtain a stabilized immunogenic composition.

[0198] Further envisaged herein is use of the stabilized immunogenic composition to immunize a subject in need thereof.

[0199] In a non-limiting exemplary embodiment, the stabilized immunogenic composition is a stabilized MMR vaccine. Thus, in some embodiments, envisaged herein is use of the stabilized MMR vaccine to immunize a subject in need thereof.

[0200] In another exemplary embodiment, the stabilized immunogenic composition is a stabilized MR vaccine. Thus, in some embodiments, envisaged herein is use of the stabilized MR vaccine to immunize a subject in need thereof.

[0201] The present disclosure further provides a method of immunizing a subject in need thereof comprising administering the stabilized immunogenic composition. [0202] In some embodiments, the envisaged herein is a method of immunizing a subject against Measles, Mumps and/or Rubella comprising administering the stabilized MMR vaccine of the present disclosure to the subject.

[0203] In some embodiments, the envisaged herein is a method of immunizing a subject against Measles and/or Rubella comprising administering the stabilized MR vaccine of the present disclosure to the subject.

[0204] In some embodiments the present disclosure provides a kit comprising the stabilized immunogenic composition of the present disclosure.

[0205] In some embodiments, the stabilized immunogenic composition in the kit is in lyophilized form.

[0206] In some embodiments, the kit may further comprise means for administration of the stabilized immunogenic composition. Examples of such means include but are not limited to a syringe.

[0207] In some embodiments, the kit may further comprise an aqueous solution such as but not limited to saline or WFI for the reconstituting the lyophilized stabilized immunogenic composition. [0208] In some embodiments, the kit may comprise means for temperature regulation.

[0209] Thus, in some embodiments, the present disclosure provides a kit comprising a first container containing the lyophilized stabilized immunogenic composition of the present disclosure and a second container containing an aqueous solution optionally saline or water for injection for reconstituting the lyophilized stabilized immunogenic composition, optionally along with a means for administration of the reconstituted stabilized immunogenic composition and/or a means for temperature regulation.

[0210] In some embodiments, the kit further comprises a manual with instructions for use of the kit.

[0211] Advantages:

• The stabilizer composition is composed of components that are easy to source and economical.

• The stabilizer composition is easy to prepare and store.

• The stabilizer composition confers long-term stability to immunogenic compositions, at various storage temperatures. • Specifically with respect to the Measles-Rubella vaccine of the present disclosure, the vaccine shows improved thermal stability of Measles and Rubella viruses for longer duration than required by the Pharmacopeia, WHO and other regulatory agencies.

[0212] It is to be understood that the foregoing descriptive matter is illustrative of the disclosure and not a limitation. While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. Those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein. Similarly, additional embodiments and features of the present disclosure will be apparent to one of ordinary skill in art based upon description provided herein.

[0213] Descriptions of well-known/conventional methods/steps and techniques are omitted so as to not unnecessarily obscure the embodiments herein. Further, the disclosure herein provides for examples illustrating the above-described embodiments, and in order to illustrate the embodiments of the present disclosure certain aspects have been employed. The examples used herein for such illustration are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the following examples should not be construed as limiting the scope of the embodiments herein.

EXAMPLES:

[0214] The following examples are provided to illustrate the invention and are merely for illustrative purposes only. The following examples should not be construed to limit the scope of the invention.

The viral strains used to demonstrate the efficacy of the stabilizer of the present application in the following examples are popular vaccine strains, having a long history of safe use, with their origin outside of India. Rubella RA27/3 Wistar strain originates from the Wistar Institute, USA (Balfour, Henry H., et al. "Evaluation of Wistar RA27/3 Rubella virus vaccine in children." American Journal of Diseases of Children 130.10 (1976): 1089-1091.). Measles Edmonston Zagreb strain originates from Institute of Immunology in Zagreb, Croatia (Ikic, Drago M. "Edmonston-Zagreb strain of Measles vaccine: epidemiologic evaluation in Yugoslavia." Reviews of Infectious Diseases 5.3 (1983): 558-563.).

Example 1: Preparation of stabilizer compositions [0215] Concentrated phosphae-citrate buffer (about 10-30X) was prepared using citric acid and disodium hydrogen orthophosphate. Hydrolyzed gelatin, Sorbitol and Trehalose were dissolved in water for injection or purified water and then Alanine, Arginine HC1, Histidine, Glycine and Proline were added to the above solution and dissolved. This was followed by addition of HSA, citro-phosphate buffer, and Magnesium sulphate. The obtained composition was then subjected to sterile filtration. Eight different stabilizer compositions were prepared for comparison. The quantity of each of the constituents referred to above in each of the stabilizer compositions is mentioned in Table 1 below.

Table 1: Constituents of the stabilizer composition

Example 2: Preparation of stabilized immunogenic composition

[0216] Based on the presentation (single dose or multi-dose), the calculated volume of Measles and Rubella virus bulk antigens were added to the cooled stabilizer composition obtained in Example 1 in a sterile environment and stirred. Edmonston Zagreb strain of Measles antigen (Mz) and RA27/3 Wistar strain of Rubella antigen were used to prepare the immunogenic composition. The volume of the immunogenic composition was made up to batch size with sterile water for injection and the stirring was continued for another about 10 - 20 minutes. The sterile final bulk (blend) was stored at about 2-8°C till filling.

[0217] Alternatively, the stabilizer solution was stored at room temperature and based on the presentation (single dose or multi-dose), the calculated volume of Measles and Rubella virus bulk antigens were added to the stabilizer solution at room temperature in a sterile environment and stirred. The volume of the immunogenic composition was made up to batch size with sterile WFI and the stirring was continued for another about 10 - 20 minutes. The sterile final bulk (blend) was stored at about 2-8°C till filling.

[0218] Based on the presentation, the required volume was filled in a suitable glass vial, partially stoppered and lyophilized. The lyophilized vials were stored at about 2-8°C. The lyophilized vials were tested for Measles and Rubella virus titer at stability, percentage moisture content, sterility and all other parameters as required by Pharmacopeia for the Measles and Rubella vaccine. The results for the stability assessment are provided below.

Example 3: Stability assessment of the stabilized immunogenic compositions

[0219] The stability of the lyophilized Measles and Rubella vaccine, prepared in accordance with Example 2, was assessed at about 37°C. The lyophilized vaccine vials were stored at about 37°C for about 21 days and reconstituted using WFI and to assess the stability. Both the Measles and Rubella virus titer in the vaccine composition, met the specification requirement for thermal stability test. The table below indicates the log reduction in viral titer over respective storage temperature and duration. The titer loss was calculated relative to the viral titer at day 0 of the test. Table 2: Stability of the stabilized immunogenic composition

[0220] In addition to the above, formulation 7 showed a log reduction in viral titer of about 0.71 for Measles and 0.36 for Rubella at 7 days post storage at 37°C. Formulation 8 on the other hand showed a log reduction in viral titer of about 0.53 for Measles and 0.18 for Rubella at 7 days post storage at 37°C.

[0221] Stable compositions are not expected to show a log reduction in viral titer of more than 1, when stored at 37°C for 7 days. Based on the above, it was seen that the exclusion of protein component HSA from the claimed composition (Formulation 4) led to a reduction in stability of the vaccine formulation, thereby indicating the synergy between the components of the stabilizer composition and the stabilized immunogenic composition of the present disclosure. Also, it was seen that using sucrose as a sugar caused the compositions to fail the thermal stability test (Formulations 5 and 6).

[0222] Further, the immunogenic compositions using the stabilizer of formulations 7 and 8 were subjected to long term stability study at 2-8°C (intended storage temperature) and tested for both Measles and Rubella virus titer at periodic intervals. Table 3 below denotes the Measles and Rubella virus titers at periodic intervals. It was seen that both Measles and Rubella virus titers met the specification requirement of not less than 3.0 log CCID50/dose, even after 36 months of storage (Figures 1 and 2). Table 3: Real-time stability data of MR vaccine

[0223] Additional embodiments and features of the present disclosure will be apparent to one of ordinary skill in art based on the description provided herein. The embodiments herein provide various features and advantageous details thereof in the description. Descriptions of well- known/conventional methods and techniques are omitted so as to not unnecessarily obscure the embodiments herein.

[0224] The foregoing description of the specific embodiments fully reveals the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments in this disclosure have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

[0225] While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the disclosure. These and other modifications in the nature of the disclosure or the preferred embodiments will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation.

[0226] All references, articles, publications, general disclosures etc. cited herein are incorporated by reference in their entireties for all purposes. However, mention of any reference, article, publication etc. cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world.

Claims

We Claim:

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.

21. The stabilized immunogenic composition as claimed in claim 19, wherein the virus(es) is selected from a group comprising Measles, Mumps, and Rubella.

22. The stabilized immunogenic composition as claimed in claim 19, wherein the virus(es) are selected from a group comprising Measles and Rubella.

23. The stabilized immunogenic composition as claimed in any of claims 19 - 22, wherein the Measles virus strain is selected from a group comprising AIK-C, Schwarz, Moraten, CAM70, TD97, Leningrad- 16, Shanghai-191, Edmonston Zagreb, a recombinant or a genetically modified form of any of these virus strains, or any combination thereof; and/or wherein the Rubella virus strain is selected from a group comprising Matsuba, DCRB19, Takahashi, Matsuura, TO-336, RA 27/3 Wistar, a recombinant or a genetically modified form of any of these virus strains, or a combination thereof.

24. The stabilized immunogenic composition as claimed in claim 23, wherein the Measles virus strain is live attenuated Edmonston Zagreb strain; and/or wherein the Rubella virus strain is live attenuated RA 27/3 Wistar strain.

25. The stabilized immunogenic composition as claimed in any one of claims 18-24, wherein the attenuated Measles virus particles is present in the range of 3.0 Log CCID50/dose to 6.0 Log CCID50/dose; and/or wherein the live attenuated Rubella virus particles is present in the range of 3.0 Log CCID50/dose to 6.0 Log CCID50/dose.

26. The stabilized immunogenic composition as claimed in any one of claims 18-25, wherein the stabilized immunogenic composition is lyophilized.

27. The stabilized immunogenic composition as claimed in any one of claims 18-26, wherein the stabilized immunogenic composition is a vaccine.

28. A method for preparing the stabilized immunogenic composition as claimed in any one of claims 18-27, comprising combining the stabilizer composition as claimed in any one of claims 1-16 with the one or more live attenuated or inactivated virus as defined in any one of claims 19-25, in presence of the carrier(s) as defined in claim 16, to obtain the stabilized immunogenic composition.

29. The method as claimed in claim 28, further comprising subjecting the stabilized immunogenic composition to lyophilization.

30. A kit comprising the stabilized immunogenic composition as claimed in any one of claims 18-28.

1. The kit as claimed in claim 30, further comprising means for administration of the stabilized immunogenic composition and/or an aqueous solution for reconstituting the stabilized immunogenic composition present in lyophilized form and/or an instruction manual.