CA1183083A - Herpes virus vaccine - Google Patents
Herpes virus vaccineInfo
- Publication number
- CA1183083A CA1183083A CA000344839A CA344839A CA1183083A CA 1183083 A CA1183083 A CA 1183083A CA 000344839 A CA000344839 A CA 000344839A CA 344839 A CA344839 A CA 344839A CA 1183083 A CA1183083 A CA 1183083A
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- Prior art keywords
- virus
- parts
- albumin
- vaccine
- stabilizer
- Prior art date
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Abstract
ABSTRACT OF THE DISCLOSURE
A new method of formulating herpes class virus vaccines, especially Marek's Disease vaccine. The virus is lyophilized in the presence of a pH controlled buffered stabilizer, so that the vaccine can be re-constituted simply with distilled water.
A new method of formulating herpes class virus vaccines, especially Marek's Disease vaccine. The virus is lyophilized in the presence of a pH controlled buffered stabilizer, so that the vaccine can be re-constituted simply with distilled water.
Description
k~"~ I.hl~
BACKGROUND OF THE INVENTION
U.S. Patent 3,783,098, issued January 1, 1974, discloses and claims a herpes virus vaccine prepared by infecting cells with the cell-associated virus, extract-ing the virus in the presence of a stab:ilizlng agent, andlyophilizing to form a storage-stable virus useful as a vaccine. Following lyophilization, the virus is re-constituted with a stabiliziny diluent. This vaccine has received substantial commercial acceptance, particularly when used ~o protect poultry against Marek's disease.
The necessity of usiny a stabilizing diluent to re constitute the lyophilized vaccinet however, increases substantially the cost of the vaccine.
DETAILED DESCRIPTION OF THE IMVENTION
It has now been discovered that a new formu-lation process can be used which makes possible the use of distilled wat~r as a diluent for the herpes virus vaccines.
In presen-t commercial practice, Mare~'s disease vaccine, is formulated with SPGA, before lyophi-lization. SPGA, a stabilizer described by Bovarnick et al., J. Ba~t. 59:509-522 (1950), is a commonly used stabilizer in commercial practice. As described by Bovarnick et al. a liter of SPGA contains 0.213 M sucrose (74.62 g), 0.00376 M KH2PO4 (0.52 g), K2~PO4 0-0071 M
(1~25 g), potassium glutamate 0.0049 M (0.912 g) and 1%
serum albumin (10 g). Various modifications of the fore-going amounts of ingredients of SPGA are known to those skilled in the art and sodium glutamate is frequently substituted for potassium glutamate, but the modified compositions are still designated as SPGA. For example, U.S. patent 3~783,098 refers to an SPGA s~abilizer con-taining monosodium glutamate rather than monopotassium glutamate (~ol. 6, lines 5-ll)o U~S~ patent 4,002,256 des-ribes an SPGA stabilizer containing per liter of - 1, 6 :1, 8 f~A
~ 2 sterile distilled water, 74.62 g sucrose, 0.~5 g KH~PO4, 1.35 g K2HPO4, 0.956 g monosodium L-glutamate, and 40 ml of a 25% solution of albuminosol (human albllmin). In general an SPGA stabilizer contains Erom about 2 to about 10% of sugar, e.g., sucrose; Erom about 0.05 to about 0.3% of a mono- or dibasic alkali metal phospha-~e salt or mixture thereof, e.g. KH2PO4, K2HPO4, NaH2PO~ or Na21lPO~;
from about 0.05 to about 0.2% of a glutamic ac:id al~a]i metal salt, e.g. sodium or potassium ylutamate; and from about 0.5% to about 2% serum albumin, e.g. bovine seYum albumin or human albumin. Various substitute ions of ingredients in the formulation of SPGA stabilizer can be made. For example, a starch hydrolysate, e~g. glucose or dextran may be substituted wholly or partly for sucrose as disclosed in U.S. patent 3,783,098 (col. 3, lines 59-61) and casein or PVP may be substituted wholly or partly for alburnin as described respectively, in U.S.
patent 3,783,0~8 (col. 3, line 8) and ~.S. patent 3,915,794. Any SPGA composition coming within the fore-going ranges of ingredients or equlvalents thereof can be used in the present invention. Aqueous compositions of SPGA when diluted to use concentrations Eor Marekls disease, that is, with sufficient water to provide 500 or 1000 doses, have a pH of from about 5.0 to about 5.7.
According to the present invention, the herpes virus ~accine is formulated at the prelyophilization stage with an SPGA stabilizer and a buffer system effective to maintain the pH of the reconstituted lyophi-lized vaccine at from about 6.8 to about 7.2 after re-constitution to use concentration. When ly~philized in the presence of such a buffer system, theAlyo~hilized virus can be reconstituted with water to form a stable, viable, vaccine. A preferred buffer system is a mixture of KH2PO4 and K2HPO4 in quantity sufficient to form on reconstitution about a 0.12 mM solution with respect to KH2PO4 and about a 0.88 m~ with respect to K2HPO4.
The virus used to prepare a vaccine to protect against Marek's disease is a turkey herpes virus. A
speci~ic example of such a vixus is the FC-126 strain (ATCC V~-58~) which is known to protect ayainst Marek's disease! Calnek et al., Appl. Microbiol. 20:723-726 (1970). The virus is administered in such a concen-tration that each individual dose (about 0~2 ml) contains at least 1,000 placlue Eorming uni-ts. It is to be uncler-stood, however, that while a particular straln is employed in the following examples, that any strain of turkey herpes virus may be used in preparing the water-reconstitutable Marek's disease vaccine of the presen-t invention. The final virus suspension is dispensed into vials for lyophilization. The amount of virus present in each vial, and so the number of doses of vaccine that can be made therefrom, is determined by assay. As an indi-vidual dose consists of about 0.2 ml, the reconstitution volume is determined by multiplying the doses per vial by 0.2 ml. As the vials usually are packaged to contain either 500 or 1,000 doses of vaccine, the vials are constituted, respectively, with either 100 or 200 ml of water.
The Eollowing examples illustrate the present invention without, however, limiting the same thereto.
E~AMPLE 1 Ten roller bottles from a production lot of turkey herpes virus (strain ATCC VR584) grown in chick embryo fibroblasts for 4 days at 38.5C in medium ll9-F10 (Gibco) with 5% sterile fetal calf serum are harvested according to standard procedures. The harvested fluid from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and 3-5 C.
The supernatant liquid is drawn off and 20.4 ml of a pH controlled buffer stabilizer (90 ml SP~A with 10 ml lM potassium phosphate buf~er pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Diluent SPGA is added to the other bottle in the same mann~r.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonicated for 2 min.
at approximately 35 watts and a temperature of 3-5C.
After sonication each sample is dispensed into 3 cc via]s (1.1 cc fill) and frozen at -70C~ for approximately 6 hours. The vials are lyophilized, sealed and labeled~
Stabllity of the 1~70philized powder is evalu-ated after storage at 37C for 3 days and reconstitution with 200 ml of distilled water. A titration assay shows that each vial contains enough virus for 1~000 doses, that is, it contains at least 1,500,000 plaque forming units. Results ar~ summarized in Table 1.
~ffect of Stabilizer on Storage Stability of Lyophilized Marek's Disease Vaccine Lyophilized Powder Titer Average Titer CompositionPFU/dose PFU/dose Run 1 Run 2 New Product 1660 2090 1895 Old Product 500 530 515 Ten roller bottles from a production lot of turkey herpes virus ~strain ATCC VR584) grown in chick embryo fibroblasts or 4 days at 38.5C in medium l99-F10 (Gibco~ with 5% sterile fetal calf serum are harvested according to standard procedures. The harvested fluid from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and 3-5 C.
The supernatant liquid is drawn off and 20.4 ml of a pH controlled buff~r stabilizer (90 ml SPGA with 10 ml lM sodi~m phosphate buffer pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Diluen~ SPGA is added to a separate , ~ 161~3~A
bottle in the same mannex.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonica-ted for 2 minutes at approximately 35 watts and a tempera~ure of 3-5C. After sonication, each sample is dispensed into 3 ml vials (1.1 ml fill) and frozen at -70C for approxi-mately 6 hours. The vials are lyophili~ed, sealed and labeled.
Stability of the lyophilized powder is evalu-ated after storage at 37C for 3 days and reconstitutionwith 200 ml of distilled watex. A titration assay shows that each vial contains enough virus for 1,000 doses, that is, it contains at least 1,500,000 plaque forming units. Results are summarized in Table 2.
Effect of Stabilizer on Storage Stability of Lyophilized Marek's Disease Vaccine Lyophilized Powder Titer Average Titer Composition PFU/dose PFU/dose Run 1 Run 2 New Product 2230 1970 2100 Old Product 500 530 515 One hundred and thirty two roller bottles from a production lot of turkey herpes virus (strain ATCC
VR584) are harvested according to standard procedure.
The harvested fluid is dispensed into conical centrifuge bottles and centrifuged for 10 minutes at 1000 RPM at 3-5C. 5upernate is drawn off and approximately 30 ml of a pH controlled buffered stabilizer (90 ml SPGA + 10 ml lM potassi~m phosphate buffer pH 7.8) is added to each of the bottles. The final volume is 700 ml. The theoreti-cal cell concentration is calculated to bP approximately 15.1 x 105 cells/mlu The 700 ml suspension is held in ice bath and sonicated using a Flow Sonicating apparatus. Following sonication, the vaccine is transferred to a metal can and L6:1~3~3A
shell frozen in an alcohol freezer and stoxed in a -70C
freezer for storage.
A week later -the can content is thawed in a water bath at 29C; final dilu-tion is made and dispensed into 3 ml ~ials (1.1 ml fill). Vials are frozen at -70C
for approximately 6 hours. The vials are lyoph:ilized, sealed and labeled.
EXAMPLE ~I
Ten roller bottles Erom a production lot of turkey herpes virus (strain ATCC VR5~) grown in chick embryo fibroblasts for 4 days at 38.5C in medium l99-F10 (Gibco) with 5~ sterile fetal calf serum are harvested according to standard procedures. The harvested fl~id from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and at 3-5C.
Supernate is drawn off and 20.~ ml of a pH
controlled buffer stabilizer (90 ml SPGA + 10 ml lM
phosphate buffer, pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Another pH controlled buffer stabilizer (90 ml SPGA + 10 ml lM phosphate buffer pH 6.2) is added to the other bot-tle in the same manner.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonicated for 2 minutes at approximately 35 watts and a temperature of 3-5C. After sonication each sample is dispensed into 3 cc vials (1.1 cc fill) and frozen at -70C for approxi-mately 6 hours. The vials are lyophilized, sealed and labeled.
Stability of the lyophilized powder is evalu-ated after storage at 37C for 3 days and reconstitution with 200 ml of distilled water. A ti~ration assay shows that Pach vial contains enough virus for 1,000 doses, that is, it contains at least 1,500,000 plaq~le forming units. Results are summarized in Table 3.
161~A
Effect of Stabilizer pH on Storage Stability oE
Lyophilized Marek's Disease Vaccine Buffer pH Ti-ter Averaye Tiker PFU/dose PFH/dose Run_ Run 2 6.2 2110 2300 2205 7.8 7360 12310 9~35 As the examples illustra-te, the vaccine pre-pared with the pH controlled buffered stabillzer has a significantly higher stahility when reconstituted with distilled water than the vaccine prepared with simple diluent stabili2er of the prior art. These examples used SPGA, a stabilizer which already contains phosphate. For instance 200 Ml of SPGA is made up of 14~92 mg, sucrose, 15 OolO mg KH2PO4, 0-32 mg K2HPO4, 0.01 gm Na glutamate, and
BACKGROUND OF THE INVENTION
U.S. Patent 3,783,098, issued January 1, 1974, discloses and claims a herpes virus vaccine prepared by infecting cells with the cell-associated virus, extract-ing the virus in the presence of a stab:ilizlng agent, andlyophilizing to form a storage-stable virus useful as a vaccine. Following lyophilization, the virus is re-constituted with a stabiliziny diluent. This vaccine has received substantial commercial acceptance, particularly when used ~o protect poultry against Marek's disease.
The necessity of usiny a stabilizing diluent to re constitute the lyophilized vaccinet however, increases substantially the cost of the vaccine.
DETAILED DESCRIPTION OF THE IMVENTION
It has now been discovered that a new formu-lation process can be used which makes possible the use of distilled wat~r as a diluent for the herpes virus vaccines.
In presen-t commercial practice, Mare~'s disease vaccine, is formulated with SPGA, before lyophi-lization. SPGA, a stabilizer described by Bovarnick et al., J. Ba~t. 59:509-522 (1950), is a commonly used stabilizer in commercial practice. As described by Bovarnick et al. a liter of SPGA contains 0.213 M sucrose (74.62 g), 0.00376 M KH2PO4 (0.52 g), K2~PO4 0-0071 M
(1~25 g), potassium glutamate 0.0049 M (0.912 g) and 1%
serum albumin (10 g). Various modifications of the fore-going amounts of ingredients of SPGA are known to those skilled in the art and sodium glutamate is frequently substituted for potassium glutamate, but the modified compositions are still designated as SPGA. For example, U.S. patent 3~783,098 refers to an SPGA s~abilizer con-taining monosodium glutamate rather than monopotassium glutamate (~ol. 6, lines 5-ll)o U~S~ patent 4,002,256 des-ribes an SPGA stabilizer containing per liter of - 1, 6 :1, 8 f~A
~ 2 sterile distilled water, 74.62 g sucrose, 0.~5 g KH~PO4, 1.35 g K2HPO4, 0.956 g monosodium L-glutamate, and 40 ml of a 25% solution of albuminosol (human albllmin). In general an SPGA stabilizer contains Erom about 2 to about 10% of sugar, e.g., sucrose; Erom about 0.05 to about 0.3% of a mono- or dibasic alkali metal phospha-~e salt or mixture thereof, e.g. KH2PO4, K2HPO4, NaH2PO~ or Na21lPO~;
from about 0.05 to about 0.2% of a glutamic ac:id al~a]i metal salt, e.g. sodium or potassium ylutamate; and from about 0.5% to about 2% serum albumin, e.g. bovine seYum albumin or human albumin. Various substitute ions of ingredients in the formulation of SPGA stabilizer can be made. For example, a starch hydrolysate, e~g. glucose or dextran may be substituted wholly or partly for sucrose as disclosed in U.S. patent 3,783,098 (col. 3, lines 59-61) and casein or PVP may be substituted wholly or partly for alburnin as described respectively, in U.S.
patent 3,783,0~8 (col. 3, line 8) and ~.S. patent 3,915,794. Any SPGA composition coming within the fore-going ranges of ingredients or equlvalents thereof can be used in the present invention. Aqueous compositions of SPGA when diluted to use concentrations Eor Marekls disease, that is, with sufficient water to provide 500 or 1000 doses, have a pH of from about 5.0 to about 5.7.
According to the present invention, the herpes virus ~accine is formulated at the prelyophilization stage with an SPGA stabilizer and a buffer system effective to maintain the pH of the reconstituted lyophi-lized vaccine at from about 6.8 to about 7.2 after re-constitution to use concentration. When ly~philized in the presence of such a buffer system, theAlyo~hilized virus can be reconstituted with water to form a stable, viable, vaccine. A preferred buffer system is a mixture of KH2PO4 and K2HPO4 in quantity sufficient to form on reconstitution about a 0.12 mM solution with respect to KH2PO4 and about a 0.88 m~ with respect to K2HPO4.
The virus used to prepare a vaccine to protect against Marek's disease is a turkey herpes virus. A
speci~ic example of such a vixus is the FC-126 strain (ATCC V~-58~) which is known to protect ayainst Marek's disease! Calnek et al., Appl. Microbiol. 20:723-726 (1970). The virus is administered in such a concen-tration that each individual dose (about 0~2 ml) contains at least 1,000 placlue Eorming uni-ts. It is to be uncler-stood, however, that while a particular straln is employed in the following examples, that any strain of turkey herpes virus may be used in preparing the water-reconstitutable Marek's disease vaccine of the presen-t invention. The final virus suspension is dispensed into vials for lyophilization. The amount of virus present in each vial, and so the number of doses of vaccine that can be made therefrom, is determined by assay. As an indi-vidual dose consists of about 0.2 ml, the reconstitution volume is determined by multiplying the doses per vial by 0.2 ml. As the vials usually are packaged to contain either 500 or 1,000 doses of vaccine, the vials are constituted, respectively, with either 100 or 200 ml of water.
The Eollowing examples illustrate the present invention without, however, limiting the same thereto.
E~AMPLE 1 Ten roller bottles from a production lot of turkey herpes virus (strain ATCC VR584) grown in chick embryo fibroblasts for 4 days at 38.5C in medium ll9-F10 (Gibco) with 5% sterile fetal calf serum are harvested according to standard procedures. The harvested fluid from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and 3-5 C.
The supernatant liquid is drawn off and 20.4 ml of a pH controlled buffer stabilizer (90 ml SP~A with 10 ml lM potassium phosphate buf~er pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Diluent SPGA is added to the other bottle in the same mann~r.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonicated for 2 min.
at approximately 35 watts and a temperature of 3-5C.
After sonication each sample is dispensed into 3 cc via]s (1.1 cc fill) and frozen at -70C~ for approximately 6 hours. The vials are lyophilized, sealed and labeled~
Stabllity of the 1~70philized powder is evalu-ated after storage at 37C for 3 days and reconstitution with 200 ml of distilled water. A titration assay shows that each vial contains enough virus for 1~000 doses, that is, it contains at least 1,500,000 plaque forming units. Results ar~ summarized in Table 1.
~ffect of Stabilizer on Storage Stability of Lyophilized Marek's Disease Vaccine Lyophilized Powder Titer Average Titer CompositionPFU/dose PFU/dose Run 1 Run 2 New Product 1660 2090 1895 Old Product 500 530 515 Ten roller bottles from a production lot of turkey herpes virus ~strain ATCC VR584) grown in chick embryo fibroblasts or 4 days at 38.5C in medium l99-F10 (Gibco~ with 5% sterile fetal calf serum are harvested according to standard procedures. The harvested fluid from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and 3-5 C.
The supernatant liquid is drawn off and 20.4 ml of a pH controlled buff~r stabilizer (90 ml SPGA with 10 ml lM sodi~m phosphate buffer pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Diluen~ SPGA is added to a separate , ~ 161~3~A
bottle in the same mannex.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonica-ted for 2 minutes at approximately 35 watts and a tempera~ure of 3-5C. After sonication, each sample is dispensed into 3 ml vials (1.1 ml fill) and frozen at -70C for approxi-mately 6 hours. The vials are lyophili~ed, sealed and labeled.
Stability of the lyophilized powder is evalu-ated after storage at 37C for 3 days and reconstitutionwith 200 ml of distilled watex. A titration assay shows that each vial contains enough virus for 1,000 doses, that is, it contains at least 1,500,000 plaque forming units. Results are summarized in Table 2.
Effect of Stabilizer on Storage Stability of Lyophilized Marek's Disease Vaccine Lyophilized Powder Titer Average Titer Composition PFU/dose PFU/dose Run 1 Run 2 New Product 2230 1970 2100 Old Product 500 530 515 One hundred and thirty two roller bottles from a production lot of turkey herpes virus (strain ATCC
VR584) are harvested according to standard procedure.
The harvested fluid is dispensed into conical centrifuge bottles and centrifuged for 10 minutes at 1000 RPM at 3-5C. 5upernate is drawn off and approximately 30 ml of a pH controlled buffered stabilizer (90 ml SPGA + 10 ml lM potassi~m phosphate buffer pH 7.8) is added to each of the bottles. The final volume is 700 ml. The theoreti-cal cell concentration is calculated to bP approximately 15.1 x 105 cells/mlu The 700 ml suspension is held in ice bath and sonicated using a Flow Sonicating apparatus. Following sonication, the vaccine is transferred to a metal can and L6:1~3~3A
shell frozen in an alcohol freezer and stoxed in a -70C
freezer for storage.
A week later -the can content is thawed in a water bath at 29C; final dilu-tion is made and dispensed into 3 ml ~ials (1.1 ml fill). Vials are frozen at -70C
for approximately 6 hours. The vials are lyoph:ilized, sealed and labeled.
EXAMPLE ~I
Ten roller bottles Erom a production lot of turkey herpes virus (strain ATCC VR5~) grown in chick embryo fibroblasts for 4 days at 38.5C in medium l99-F10 (Gibco) with 5~ sterile fetal calf serum are harvested according to standard procedures. The harvested fl~id from these roller bottles is split into 2 conical cen-trifuge bottles and centrifuged for 10 minutes at 1000 RPM and at 3-5C.
Supernate is drawn off and 20.~ ml of a pH
controlled buffer stabilizer (90 ml SPGA + 10 ml lM
phosphate buffer, pH 7.8) is added to one bottle to attain a theoretical cell concentration of 20 x 106 cells. Another pH controlled buffer stabilizer (90 ml SPGA + 10 ml lM phosphate buffer pH 6.2) is added to the other bot-tle in the same manner.
The contents of each of the two bottles are dispensed into 30 ml vials and batch sonicated for 2 minutes at approximately 35 watts and a temperature of 3-5C. After sonication each sample is dispensed into 3 cc vials (1.1 cc fill) and frozen at -70C for approxi-mately 6 hours. The vials are lyophilized, sealed and labeled.
Stability of the lyophilized powder is evalu-ated after storage at 37C for 3 days and reconstitution with 200 ml of distilled water. A ti~ration assay shows that Pach vial contains enough virus for 1,000 doses, that is, it contains at least 1,500,000 plaq~le forming units. Results are summarized in Table 3.
161~A
Effect of Stabilizer pH on Storage Stability oE
Lyophilized Marek's Disease Vaccine Buffer pH Ti-ter Averaye Tiker PFU/dose PFH/dose Run_ Run 2 6.2 2110 2300 2205 7.8 7360 12310 9~35 As the examples illustra-te, the vaccine pre-pared with the pH controlled buffered stabillzer has a significantly higher stahility when reconstituted with distilled water than the vaccine prepared with simple diluent stabili2er of the prior art. These examples used SPGA, a stabilizer which already contains phosphate. For instance 200 Ml of SPGA is made up of 14~92 mg, sucrose, 15 OolO mg KH2PO4, 0-32 mg K2HPO4, 0.01 gm Na glutamate, and
2.0 gm albuminO By contrast, the dry weights of these components in 1 vial of our new vaccine product (to be diluted with 200 ml water~ is 73~9 mg sucrose, 3.4 mg KH2PO4, 16.6 mg K2HPO4, 0.9 mg Na glutamate, and 9.9 mg albumin. We have calculated that as long as a preferred level of about 20 mg of total phosphate buffer is present in a finished vaccine vial, any stabilizer can be used during lyophilization. Obviously calculations can be made by the user. We have further determined that be-tween about 10-60 mg per finished vial of to-tal phosphate buffer can be operably employed. In parts by weight per liter the compositions of the present invention contain from about 33 to about 135 parts sucrose, from about 1.5 to about 15 parts KH2PO4, from about 7 to about 30 parts 30 K2HPO4, from about 0.4 to about 0.17 part monosodium glutamate, and from about 4.5 to about 18 parts albumin.
Within these ranges, the ratio K2HPO4 to KH2PO4 should be 10 to 2, and is preferably about 5. &iven these figures, adjustments to any commonly used stabilizer system can be made to yield the stabilized vaccine of this invention, having the advantage of being easily diluted for use with distilled water.
Within these ranges, the ratio K2HPO4 to KH2PO4 should be 10 to 2, and is preferably about 5. &iven these figures, adjustments to any commonly used stabilizer system can be made to yield the stabilized vaccine of this invention, having the advantage of being easily diluted for use with distilled water.
Claims (7)
1. A composition comprising a lyophllized, cell-free turkey herpes virus, a herpes virus stabilizer containing at least one member selected from sucrose, glucose or dextran, glutamine and at least one member selected from albumin, casein or polyvinylpyrrolidone and an amount of phosphate buffer effective to maintain the pH at from about 6.8 to about 7.2 after reconsti-tution of the virus to use level by the addition of from about 100 to about 200 volumes of water.
2. The composition of Claim 1, wherein the virus is strain ATCC VR-584.
3. The composition of Claim 1, wherein the stabilizer comprises sucrose, phosphate, glutamine and albumin.
4. An aqueous mixture comprising the re-constituted composition of Claim 1.
5. The mixture of Claim 4, wherein the virus is strain ATCC VR-584.
6. The mixture of Claim 4, wherein the stabilizer comprises sucrose, phosphate, glutamine and albumin.
7. The suspension of Claim 6 comprising in parts by weight per 1000 parts water, from about 33 to about 135 parts sucrose, from about 1.5 to about 15 parts KH2PO4, from about 7 to about 30 parts K2HPO4, from about 0.4 to about 0.17 part monosodium glutamate, and from about 4.5 to about 18 parts albumin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000344839A CA1183083A (en) | 1980-01-31 | 1980-01-31 | Herpes virus vaccine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000344839A CA1183083A (en) | 1980-01-31 | 1980-01-31 | Herpes virus vaccine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1183083A true CA1183083A (en) | 1985-02-26 |
Family
ID=4116150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000344839A Expired CA1183083A (en) | 1980-01-31 | 1980-01-31 | Herpes virus vaccine |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1183083A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5066492A (en) * | 1986-03-05 | 1991-11-19 | University Of Birmingham | Method of treating herpes simplex virus |
-
1980
- 1980-01-31 CA CA000344839A patent/CA1183083A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5066492A (en) * | 1986-03-05 | 1991-11-19 | University Of Birmingham | Method of treating herpes simplex virus |
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