WO2024107677A1 - Salmonella vaccine compositions and methods thereof - Google Patents
Salmonella vaccine compositions and methods thereof Download PDFInfo
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- WO2024107677A1 WO2024107677A1 PCT/US2023/079569 US2023079569W WO2024107677A1 WO 2024107677 A1 WO2024107677 A1 WO 2024107677A1 US 2023079569 W US2023079569 W US 2023079569W WO 2024107677 A1 WO2024107677 A1 WO 2024107677A1
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- salmonella
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- 238000000034 method Methods 0.000 title claims abstract description 169
- 239000000203 mixture Substances 0.000 title claims abstract description 37
- 229940124842 Salmonella vaccine Drugs 0.000 title description 2
- 229960005486 vaccine Drugs 0.000 claims abstract description 166
- 239000000427 antigen Substances 0.000 claims abstract description 124
- 102000036639 antigens Human genes 0.000 claims abstract description 124
- 108091007433 antigens Proteins 0.000 claims abstract description 124
- 241001437644 Salmonella enterica subsp. enterica serovar Kentucky Species 0.000 claims abstract description 66
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 claims abstract description 66
- 241001465754 Metazoa Species 0.000 claims description 81
- 241000607142 Salmonella Species 0.000 claims description 57
- 241000894006 Bacteria Species 0.000 claims description 50
- 241000287828 Gallus gallus Species 0.000 claims description 45
- 230000028993 immune response Effects 0.000 claims description 32
- 241000271566 Aves Species 0.000 claims description 18
- 206010039438 Salmonella Infections Diseases 0.000 claims description 18
- 206010039447 salmonellosis Diseases 0.000 claims description 18
- 208000015181 infectious disease Diseases 0.000 claims description 17
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 241000272525 Anas platyrhynchos Species 0.000 claims description 6
- 238000010255 intramuscular injection Methods 0.000 claims description 6
- 239000007927 intramuscular injection Substances 0.000 claims description 6
- 238000010254 subcutaneous injection Methods 0.000 claims description 6
- 239000007929 subcutaneous injection Substances 0.000 claims description 6
- 210000000936 intestine Anatomy 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 3
- 235000013330 chicken meat Nutrition 0.000 description 29
- 239000003921 oil Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 5
- 241000607128 Salmonella enterica subsp. enterica serovar Infantis Species 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 229940031416 bivalent vaccine Drugs 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0275—Salmonella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
Definitions
- Salmonella is a genus of Gram-negative bacteria belonging to the family Enterobacteriaceae. Salmonella species are intracellular pathogens of animals and certain serotypes can potentially cause illness in animals. For instance, Salmonella infections can be the result of a foodbourne illness potentially caused by a Group B bacterium, a Group C bacterium, and/or a Group D bacterium.
- Vaccination of animals is important to prevent Salmonella infections.
- vaccines that will provide cross-protection against multiple groups of Salmonella bacteria (e.g., Group B, Group C, and Group D) are highly desirable.
- an inactivated bivalent vaccine offering synergistic effects and/or cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection is currently not available.
- compositions comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen that provide desired cross-protection.
- Vaccines and kits comprising the multiple antigen compositions are also provided, as well as methods of administering the vaccine to non-human animals.
- a composition comprising i) a first antigen and ii) a second antigen, wherein the first antigen is an inactivated Salmonella typhimurium antigen and the second antigen is an inactivated Salmonella kentucky antigen.
- an inactivated antigen is generally known as a non-living antigen of a pathogen and thus cannot replicate.
- the composition provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
- the composition provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection.
- cross-protection refers to protection against an infection or disease due to an immune response that is elicited against a related infection/disease.
- a vaccine comprises i) an effective amount of an inactivated Salmonella typhimurium antigen, ii) an effective amount of an inactivated Salmonella kentucky antigen, and an adjuvant.
- the adjuvant is water-in-oil. In an embodiment, the vaccine further comprises a water-in-oil (W/O) component. In an embodiment, the adjuvant is water-in- oil-in-water. In an embodiment, the vaccine further comprises a water-in-oil-in-water (W/O/W) component.
- the vaccine is configured as a multi-dose vial.
- the vaccine provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
- the vaccine provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection.
- kits comprising the vaccine as described herein and one or more vials, wherein the vaccine is contained in the one or more vials.
- a vial can refer to a glass bottle, a plastic bottle, and other types of bottles.
- the kit further comprises a syringe.
- the kit further comprises materials to substantially maintain the kit at a temperature between 2 °C and 8 °C. In an embodiment, the temperature is maintained for at least a period of time between 1 day and 7 days.
- the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 6 months. In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 12 months. In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 18 months. In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 24 months. Without being bound by any theory, the kit may maintain the ability to induce an immune response and/or maintain an efficacy when maintained at a temperature between 2 °C and 8 °C.
- the inactivated Salmonella typhimurium antigen and the inactivated Salmonella kentucky antigen are contained in the same vial.
- the kit comprises at least two vials, wherein a first vial contains the inactivated Salmonella typhimurium antigen and a second vial contains the inactivated Salmonella kentucky antigen.
- the kit further comprises a second veterinary composition.
- the second veterinary composition is a second vaccine.
- a second vaccine can provide further protection against an infection or disease caused by a different organism.
- the second vaccine can be AviPro® 109 SE4 or another vaccine against a bacterium, including Salmonella bacteria.
- the second vaccine comprises a Salmonella enteritidis bacterium. In an embodiment, the second vaccine comprises a Salmonella infantis bacterium.
- a method of administering a vaccine to a non-human animal comprises a step of administering to the animal an effective amount of the vaccine as described herein.
- the method provides at least 85% efficacy against a Salmonella infection.
- efficacy against a Salmonella infection can refer to the presence or absence of Salmonella colonization in the animal.
- efficacy against a Salmonella infection can be shown via the absence of Salmonella colonization in the animal.
- 85% efficacy against a Salmonella infection indicates that 85% of animals did not have Salmonella colonization (e.g., 17 out of 20 animals did not have Salmonella colonization, 34 out of 40 animals did not have Salmonella colonization, 85 out of 100 animals did not have Salmonella colonization, etc.).
- use of the term “protection” against a Salmonella infection can indicate that animals did not have Salmonella colonization.
- the Salmonella infection is caused by a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof.
- the method provides at least 90% efficacy. In an embodiment, the method provides at least 95% efficacy. In an embodiment, the method provides efficacy in one or more organs of the non-human animal. In an embodiment, the method provides efficacy in intestine of the nonhuman animal.
- the animal is an avian.
- the avian is selected from the group consisting of a chicken, a turkey, and a duck.
- the avian is a chicken.
- the chicken is a broiler chicken.
- the chicken is a layer chicken.
- the administration is a subcutaneous injection. In an embodiment, the administration is an intramuscular injection.
- the administration is performed when the animal is about 12 weeks of age. In an embodiment, the administration is performed when the animal is about 16 weeks of age. In an embodiment, the administration is performed when the animal is about 20 weeks of age.
- the administration is performed on the animal two or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
- the administration is performed on the animal three or more times.
- the first administration is performed when the animal is about 12 weeks of age
- the second administration is performed when the animal is about 16 weeks of age
- the third administration is performed when the animal is about 20 weeks of age.
- the administration is performed during molting of the animal. In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
- the effective amount of the vaccine is between about 0.1 ml to about 1 ml. In an embodiment, the effective amount of the vaccine is about 0.10 ml. In an embodiment, the effective amount of the vaccine is about 0.25 ml. In an embodiment, the effective amount of the vaccine is about 0.50 ml. In an embodiment, the effective amount of the vaccine is about 0.75 ml. In an embodiment, the effective amount of the vaccine is about 1 ml.
- the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 10 6 and 1 x 10 10 total cell count (TCC). In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 6 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 7 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 8 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 9 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x IO 10 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 10 6 and 1 x IO 10 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 6 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 7 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 8 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 9 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x IO 10 TCC.
- the method further comprises administration of a second veterinary composition.
- the second veterinary composition is a second vaccine.
- the second vaccine comprises a Salmonella Enteritidis bacterin.
- a method of inducing an immune response in a nonhuman animal comprises a step of administering to the animal an effective amount of the vaccine as described herein.
- the immune response is against one or more of a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof. In an embodiment, the immune response is against a Salmonella Group B bacterium. In an embodiment, the immune response is against a Salmonella Group C bacterium. In an embodiment, the immune response is against a Salmonella Group D bacterium.
- the immune response is against an inactivated Salmonella typhimurium antigen. In an embodiment, the immune response is against an inactivated Salmonella kentucky antigen. In an embodiment, the immune response comprises an immune response against an inactivated Salmonella typhimurium antigen and an immune response against an inactivated Salmonella kentucky antigen.
- the animal is an avian.
- the avian is selected from the group consisting of a chicken, a turkey, and a duck.
- the avian is a chicken.
- the chicken is a broiler chicken.
- the chicken is a layer chicken.
- the administration is a subcutaneous injection. In an embodiment, the administration is an intramuscular injection.
- the administration is performed when the animal is about 12 weeks of age. In an embodiment, the administration is performed when the animal is about 16 weeks of age. In an embodiment, the administration is performed when the animal is about 20 weeks of age.
- the administration is performed on the animal two or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
- the administration is performed on the animal three or more times.
- the first administration is performed when the animal is about 12 weeks of age
- the second administration is performed when the animal is about 16 weeks of age
- the third administration is performed when the animal is about 20 weeks of age.
- the administration is performed during molting of the animal. In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
- the effective amount of the vaccine is between about 0. 1 ml to about 1 ml. In an embodiment, the effective amount of the vaccine is about 0.10 ml. In an embodiment, the effective amount of the vaccine is about 0.25 ml. In an embodiment, the effective amount of the vaccine is about 0.50 ml. In an embodiment, the effective amount of the vaccine is about 0.75 ml. In an embodiment, the effective amount of the vaccine is about 1 ml.
- the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 10 6 and 1 x 10 10 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 6 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 7 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 8 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 10 9 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x IO 10 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 10 6 and 1 x IO 10 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 6 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 7 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 8 TCC.
- the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 10 9 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x IO 10 TCC.
- the method further comprises administration of a second veterinary composition.
- the second veterinary composition is a second vaccine.
- the second vaccine comprises a Salmonella Enteritidis bacterin.
- a composition comprising i) a first antigen and ii) a second antigen, wherein the first antigen is an inactivated Salmonella typhimurium antigen and wherein the second antigen is an inactivated Salmonella kentucky antigen.
- composition of clause 1, any other suitable clause, or any combination of suitable clauses wherein the composition provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
- a vaccine comprising i) an effective amount of an inactivated Salmonella typhimurium antigen, ii) an effective amount of an inactivated Salmonella kentucky antigen, and an adjuvant. 5.
- a kit comprising the vaccine of any of clauses 4-1 1 and one or more vials, wherein the vaccine is contained in the one or more vials.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises a syringe.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises materials to substantially maintain the kit at a temperature between 2 °C and 8 °C.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 6 months.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 12 months.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 18 months.
- kit of clause 12, any other suitable clause, or any combination of suitable clauses wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 24 months.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit comprises at least two vials.
- kit of clause 12 any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises a second veterinary composition.
- a method of administering a vaccine to a non-human animal comprising a step of administering to the animal an effective amount of the vaccine of any of clauses 4-11.
- a method of inducing an immune response in a non-human animal comprising a step of administering to the animal an effective amount of a vaccine of any of clauses 4-11.
- the instant example describes an exemplary method for making a vaccine of the present disclosure.
- This example provides an exemplary method for making a water-in-oil vaccine.
- An oil phase was prepared by combining mineral oil and Span 80 and then mixing the combination for at least 10 minutes using a magnetic stir bar. The resultant oil phase was then filter sterilized under aseptic conditions.
- An aqueous phase was prepared by combining buffered saline, 40% Tween, formalin, an inactivated Salmonella typhimurium antigen, and is an inactivated Salmonella kentucky antigen. This combination was mixed for at least 5 minutes using a magnetic stir bar.
- the oil phase and the aqueous phase were then emulsified.
- the oil phase was transferred into a Kady Mill mixing vessel. Mixing was initiated and then the aqueous phase was slowly added to the oil phase to create the emulsion. After at least 15 minutes of mixing, the emulsion was aseptically transferred into vials for later use as vaccine.
- the efficacy of vaccines of the present disclosure were evaluated.
- the exemplary vaccines used in the instant example were vaccines comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen.
- W/O vaccines Three different water-in-oil (W/O) vaccines were prepared with each vaccine comprising a different dosage of Salmonella typhimurium antigen and Salmonella kentucky antigen.
- the different doses included i) 1.0 x 10 8 tcc of Salmonella typhimurium antigen and 1.0 x 10 8 tcc of Salmonella kentucky antigen per dose; ii) 5.0 x 10 8 tcc of Salmonella typhimurium antigen and 5.0 x 10 8 tcc of Salmonella kentucky antigen per dose; and iii) 1.0 x 10 9 tcc of Salmonella typhimurium antigen and 1.0 x 10 9 tcc of Salmonella kentucky antigen per dose.
- W/O/W water-in-oil-in-water
- Salmonella typhimurium antigen 1.0 x 10 9 tcc of Salmonella kentucky antigen per dose.
- a control W/O vaccine that did not comprise Salmonella typhimurium antigen or Salmonella kentucky antigen was also prepared.
- the chickens in each treatment group were administered the vaccine twice (one administration at 12 weeks of age and a second administration at 16 weeks of age. Thereafter, the efficacy of vaccine in each treatment group was evaluated by challenging the chickens at 20 weeks of age with both Salmonella typhimurium and Salmonella kentucky. Following the challenge, chickens were analyzed for “reisolation” of Salmonella typhimurium in intestine and in organs. Chickens observed to be negative for reisolation of Salmonella typhimurium were determined to be protected by the vaccine. Following the challenge, chickens were also analyzed for reisolation of Salmonella kentucky in intestine. Chickens observed to be negative for reisolation of Salmonella kentucky were determined to be protected by the vaccine.
- Table 2 shows the results of vaccine efficacy following Salmonella typhimurium challenge. Table 2. Efficacy of Vaccine Following Salmonella typhimurium Challenge
- Table 3 shows the results of vaccine efficacy following Salmonella kentucky challenge.
- the instant example demonstrates that the exemplary vaccines were effective in providing cross-protection to chickens following a challenge with Salmonella typhimurium and Salmonella kentucky.
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Abstract
The present disclosure provides compositions comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen that provide desired cross protection. Vaccines and kits comprising the multiple antigen compositions are also provided, as well as methods of administering the vaccine to non-human animals.
Description
SALMONELLA VACCINE COMPOSITIONS AND METHODS THEREOF
CROSS-REFERENCE TO RELATED APPLICAITONS
This application claims the benefit under 35 USC § 119(e) of U.S. Provisional Application Serial No. 63/425,066, filed on November 14, 2022, the entire disclosure of which is incorporated herein by reference.
TECHNICAL FIELD
The disclosure relates to compositions comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen. Vaccines, kits, and methods utilizing the same are also provided.
BACKGROUND AND SUMMARY OF THE INVENTION
Salmonella is a genus of Gram-negative bacteria belonging to the family Enterobacteriaceae. Salmonella species are intracellular pathogens of animals and certain serotypes can potentially cause illness in animals. For instance, Salmonella infections can be the result of a foodbourne illness potentially caused by a Group B bacterium, a Group C bacterium, and/or a Group D bacterium.
Vaccination of animals is important to prevent Salmonella infections. In particular, vaccines that will provide cross-protection against multiple groups of Salmonella bacteria (e.g., Group B, Group C, and Group D) are highly desirable. For example, an inactivated bivalent vaccine offering synergistic effects and/or cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection is currently not available.
Accordingly, the present disclosure provides compositions comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen that provide desired cross-protection. Vaccines and kits comprising the multiple antigen compositions are also provided, as well as methods of administering the vaccine to non-human animals.
DETAILED DESCRIPTION
Various embodiments are described herein as follows. In an illustrative aspect, a composition is provided. The composition comprises i) a first antigen and ii) a second antigen,
wherein the first antigen is an inactivated Salmonella typhimurium antigen and the second antigen is an inactivated Salmonella kentucky antigen.
An inactivated antigen is generally known as a non-living antigen of a pathogen and thus cannot replicate. In an embodiment, the composition provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium. In an embodiment, the composition provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection. Generally, cross-protection refers to protection against an infection or disease due to an immune response that is elicited against a related infection/disease.
In an illustrative aspect, a vaccine is provided. The vaccine comprises i) an effective amount of an inactivated Salmonella typhimurium antigen, ii) an effective amount of an inactivated Salmonella kentucky antigen, and an adjuvant.
In an embodiment, the adjuvant is water-in-oil. In an embodiment, the vaccine further comprises a water-in-oil (W/O) component. In an embodiment, the adjuvant is water-in- oil-in-water. In an embodiment, the vaccine further comprises a water-in-oil-in-water (W/O/W) component.
In an embodiment, the vaccine is configured as a multi-dose vial. In an embodiment, the vaccine provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium. In an embodiment, the vaccine provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection.
In an illustrative aspect, a kit is provided. The kit comprises the vaccine as described herein and one or more vials, wherein the vaccine is contained in the one or more vials.
A vial can refer to a glass bottle, a plastic bottle, and other types of bottles. In an embodiment, the kit further comprises a syringe.
In an embodiment, the kit further comprises materials to substantially maintain the kit at a temperature between 2 °C and 8 °C. In an embodiment, the temperature is maintained for at least a period of time between 1 day and 7 days.
In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 6 months. In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 12 months. In an embodiment, the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 18 months. In an embodiment, the kit is
capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 24 months. Without being bound by any theory, the kit may maintain the ability to induce an immune response and/or maintain an efficacy when maintained at a temperature between 2 °C and 8 °C.
In an embodiment, the inactivated Salmonella typhimurium antigen and the inactivated Salmonella kentucky antigen are contained in the same vial. In an embodiment, the kit comprises at least two vials, wherein a first vial contains the inactivated Salmonella typhimurium antigen and a second vial contains the inactivated Salmonella kentucky antigen.
In an embodiment, the kit further comprises a second veterinary composition. In an embodiment, the second veterinary composition is a second vaccine. For instance, a second vaccine can provide further protection against an infection or disease caused by a different organism. For example, the second vaccine can be AviPro® 109 SE4 or another vaccine against a bacterium, including Salmonella bacteria.
In an embodiment, the second vaccine comprises a Salmonella enteritidis bacterium. In an embodiment, the second vaccine comprises a Salmonella infantis bacterium.
In an illustrative aspect, a method of administering a vaccine to a non-human animal is provided. The method comprises a step of administering to the animal an effective amount of the vaccine as described herein.
In an embodiment, the method provides at least 85% efficacy against a Salmonella infection. As described herein, efficacy against a Salmonella infection can refer to the presence or absence of Salmonella colonization in the animal. For instance, efficacy against a Salmonella infection can be shown via the absence of Salmonella colonization in the animal. According to an exemplary embodiment, 85% efficacy against a Salmonella infection indicates that 85% of animals did not have Salmonella colonization (e.g., 17 out of 20 animals did not have Salmonella colonization, 34 out of 40 animals did not have Salmonella colonization, 85 out of 100 animals did not have Salmonella colonization, etc.). Similarly, use of the term “protection” against a Salmonella infection can indicate that animals did not have Salmonella colonization.
In an embodiment, the Salmonella infection is caused by a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof. In an embodiment, the method provides at least 90% efficacy. In an embodiment, the method provides at least 95% efficacy.
In an embodiment, the method provides efficacy in one or more organs of the non-human animal. In an embodiment, the method provides efficacy in intestine of the nonhuman animal.
In an embodiment, the animal is an avian. In an embodiment, the avian is selected from the group consisting of a chicken, a turkey, and a duck. In an embodiment, the avian is a chicken. In an embodiment, the chicken is a broiler chicken. In an embodiment, the chicken is a layer chicken.
In an embodiment, the administration is a subcutaneous injection. In an embodiment, the administration is an intramuscular injection.
In an embodiment, the administration is performed when the animal is about 12 weeks of age. In an embodiment, the administration is performed when the animal is about 16 weeks of age. In an embodiment, the administration is performed when the animal is about 20 weeks of age.
In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
In an embodiment, the administration is performed on the animal three or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, the second administration is performed when the animal is about 16 weeks of age, and the third administration is performed when the animal is about 20 weeks of age.
In an embodiment, the administration is performed during molting of the animal. In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
In an embodiment, the effective amount of the vaccine is between about 0.1 ml to about 1 ml. In an embodiment, the effective amount of the vaccine is about 0.10 ml. In an embodiment, the effective amount of the vaccine is about 0.25 ml. In an embodiment, the effective amount of the vaccine is about 0.50 ml. In an embodiment, the effective amount of the vaccine is about 0.75 ml. In an embodiment, the effective amount of the vaccine is about 1 ml.
In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x 1010 total cell count (TCC). In an embodiment, the effective amount of the vaccine comprises an inactivated
Salmonella typhimurium antigen at a dose of about 1 x 106 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 107 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 108 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 109 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x IO10 TCC.
In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x IO10 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 106 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 107 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 108 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 109 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x IO10 TCC.
In an embodiment, the method further comprises administration of a second veterinary composition. In an embodiment, the second veterinary composition is a second vaccine. In an embodiment, the second vaccine comprises a Salmonella Enteritidis bacterin.
In an illustrative aspect, a method of inducing an immune response in a nonhuman animal is provided. The method comprises a step of administering to the animal an effective amount of the vaccine as described herein.
In an embodiment, the immune response is against one or more of a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof. In an embodiment, the immune response is against a Salmonella Group B bacterium. In an embodiment, the immune response is against a Salmonella Group C bacterium. In an embodiment, the immune response is against a Salmonella Group D bacterium.
In an embodiment, the immune response is against an inactivated Salmonella typhimurium antigen. In an embodiment, the immune response is against an inactivated Salmonella kentucky antigen. In an embodiment, the immune response comprises an immune
response against an inactivated Salmonella typhimurium antigen and an immune response against an inactivated Salmonella kentucky antigen.
In an embodiment, the animal is an avian. In an embodiment, the avian is selected from the group consisting of a chicken, a turkey, and a duck. In an embodiment, the avian is a chicken. In an embodiment, the chicken is a broiler chicken. In an embodiment, the chicken is a layer chicken.
In an embodiment, the administration is a subcutaneous injection. In an embodiment, the administration is an intramuscular injection.
In an embodiment, the administration is performed when the animal is about 12 weeks of age. In an embodiment, the administration is performed when the animal is about 16 weeks of age. In an embodiment, the administration is performed when the animal is about 20 weeks of age.
In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
In an embodiment, the administration is performed on the animal three or more times. In an embodiment, the first administration is performed when the animal is about 12 weeks of age, the second administration is performed when the animal is about 16 weeks of age, and the third administration is performed when the animal is about 20 weeks of age.
In an embodiment, the administration is performed during molting of the animal. In an embodiment, the administration is performed on the animal two or more times. In an embodiment, the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
In an embodiment, the effective amount of the vaccine is between about 0. 1 ml to about 1 ml. In an embodiment, the effective amount of the vaccine is about 0.10 ml. In an embodiment, the effective amount of the vaccine is about 0.25 ml. In an embodiment, the effective amount of the vaccine is about 0.50 ml. In an embodiment, the effective amount of the vaccine is about 0.75 ml. In an embodiment, the effective amount of the vaccine is about 1 ml.
In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x 1010 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 106 TCC. In an embodiment, the effective amount
of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 107 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 108 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 109 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x IO10 TCC.
In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x IO10 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 106 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 107 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 108 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 109 TCC. In an embodiment, the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x IO10 TCC.
In an embodiment, the method further comprises administration of a second veterinary composition. In an embodiment, the second veterinary composition is a second vaccine. In an embodiment, the second vaccine comprises a Salmonella Enteritidis bacterin.
The following numbered embodiments are contemplated and are non-limiting:
1. A composition comprising i) a first antigen and ii) a second antigen, wherein the first antigen is an inactivated Salmonella typhimurium antigen and wherein the second antigen is an inactivated Salmonella kentucky antigen.
2. The composition of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the composition provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
3. The composition of clause 1, any other suitable clause, or any combination of suitable clauses, wherein the composition provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection.
4. A vaccine comprising i) an effective amount of an inactivated Salmonella typhimurium antigen, ii) an effective amount of an inactivated Salmonella kentucky antigen, and an adjuvant.
5. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, wherein the adjuvant is water-in-oil.
6. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, further comprising a water-in-oil (W/O) component.
7. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, wherein the adjuvant is water-in-oil-in-water.
8. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, further comprising a water-in-oil-in-water (W/O/W) component.
9. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, wherein the vaccine is configured as a multi-dose vial.
10. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, wherein the vaccine provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
11. The vaccine of clause 4, any other suitable clause, or any combination of suitable clauses, wherein the vaccine provides cross-protection against a Salmonella lyphimurium infection and a Salmonella kentucky infection.
12. A kit comprising the vaccine of any of clauses 4-1 1 and one or more vials, wherein the vaccine is contained in the one or more vials.
13. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises a syringe.
14. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises materials to substantially maintain the kit at a temperature between 2 °C and 8 °C.
15. The kit of clause 14, any other suitable clause, or any combination of suitable clauses, wherein the temperature is maintained for at least a period of time between 1 day and 7 days.
16. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 6 months.
17. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 12 months.
18. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 18 months.
19. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit is capable of being maintained at a temperature between 2 °C and 8 °C for at least a period of time of 24 months.
20. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the inactivated Salmonella typhimurium antigen and the inactivated Salmonella kentucky antigen are contained in the same vial.
21. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit comprises at least two vials.
22. The kit of clause 21, any other suitable clause, or any combination of suitable clauses, wherein one vial contains the inactivated Salmonella typhimurium antigen.
23. The kit of clause 21, any other suitable clause, or any combination of suitable clauses, wherein one vial contains the inactivated Salmonella kentucky antigen.
24. The kit of clause 21, any other suitable clause, or any combination of suitable clauses, wherein a first vial contains the inactivated Salmonella typhimurium antigen and a second vial contains the inactivated Salmonella kentucky antigen.
25. The kit of clause 12, any other suitable clause, or any combination of suitable clauses, wherein the kit further comprises a second veterinary composition.
26. The kit of clause 25, any other suitable clause, or any combination of suitable clauses, wherein the second veterinary composition is a second vaccine.
27. The kit of clause 26, any other suitable clause, or any combination of suitable clauses, wherein the second vaccine comprises a Salmonella enteritidis bacterium or a Salmonella infantis bacterium.
28. The kit of clause 26, any other suitable clause, or any combination of suitable clauses, wherein the second vaccine comprises a Salmonella enteritidis bacterium.
29. The kit of clause 26, any other suitable clause, or any combination of suitable clauses, wherein the second vaccine comprises a Salmonella infantis bacterium.
30. A method of administering a vaccine to a non-human animal, said method comprising a step of administering to the animal an effective amount of the vaccine of any of clauses 4-11.
31. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the method provides at least 85% efficacy against a Salmonella infection.
32. The method of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the Salmonella infection is caused by a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof.
33. The method of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the method provides at least 90% efficacy.
34. The method of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the method provides at least 95% efficacy.
35. The method of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the method provides efficacy in one or more organs of the non-human animal.
36. The method of clause 31, any other suitable clause, or any combination of suitable clauses, wherein the method provides efficacy in intestine of the non-human animal.
37. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the animal is an avian.
38. The method of clause 37, any other suitable clause, or any combination of suitable clauses, wherein the avian is selected from the group consisting of a chicken, a turkey, and a duck.
39. The method of clause 37, any other suitable clause, or any combination of suitable clauses, wherein the avian is a chicken.
40. The method of clause 39, any other suitable clause, or any combination of suitable clauses, wherein the chicken is a broiler chicken.
41. The method of clause 39, any other suitable clause, or any combination of suitable clauses, wherein the chicken is a layer chicken.
42. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is a subcutaneous injection.
43. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is an intramuscular injection.
44. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed when the animal is about 12 weeks of age.
45. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed when the animal is about 16 weeks of age.
46. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed when the animal is about 20 weeks of age.
47. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times.
48. The method of clause 47, any other suitable clause, or any combination of suitable clauses, wherein the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
49. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal three or more times.
50. The method of clause 49, any other suitable clause, or any combination of suitable clauses, wherein the first administration is performed when the animal is about 12 weeks of age, the second administration is performed when the animal is about 16 weeks of age, and the third administration is performed when the animal is about 20 weeks of age.
51. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed during molting of the animal.
52. The method of clause 51, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times.
53. The method of clause 51, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
54. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is between about 0.1 ml to about 1 ml.
55. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0. 10 ml.
56. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.25 ml.
57. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.50 ml.
58. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.75 ml.
59. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 1 ml.
60. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x 10luTCC.
61. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 106 TCC.
62. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 107 TCC.
63. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 108 TCC.
64. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 109 TCC.
65. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x IO10 TCC.
66. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x 1010 TCC.
67. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 106 TCC.
68. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 107 TCC.
69. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 108 TCC.
70. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky’ antigen at a dose of about 1 x 109 TCC.
71. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 1010 TCC.
72. The method of clause 30, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second veterinary composition.
73. The method of clause 72, any other suitable clause, or any combination of suitable clauses, wherein the second veterinary composition is a second vaccine.
74. The method of clause 73, any other suitable clause, or any combination of suitable clauses, wherein the second vaccine comprises a Salmonella Enteritidis bacterin.
75. A method of inducing an immune response in a non-human animal, said method comprising a step of administering to the animal an effective amount of a vaccine of any of clauses 4-11.
76. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against one or more of a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof.
77. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against a Salmonella Group B bacterium.
78. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against a Salmonella Group C bacterium.
79. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against a Salmonella Group D bacterium.
80. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against an inactivated Salmonella typhimurium antigen.
81. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response is against an inactivated Salmonella kentucky antigen.
82. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the immune response comprises an immune response against an inactivated Salmonella typhimurium antigen and an immune response against an inactivated Salmonella kentucky antigen.
83. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the animal is an avian.
84. The method of clause 83, any other suitable clause, or any combination of suitable clauses, wherein the avian is selected from the group consisting of a chicken, a turkey, and a duck.
85. The method of clause 83, any other suitable clause, or any combination of suitable clauses, wherein the avian is a chicken.
86. The method of clause 85, any other suitable clause, or any combination of suitable clauses, wherein the chicken is a broiler chicken.
87. The method of clause 85, any other suitable clause, or any combination of suitable clauses, wherein the chicken is a layer chicken.
88. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is a subcutaneous injection.
89. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is an intramuscular injection.
90. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed when the animal is about 12 weeks of age.
91 . The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed when the animal is about 16 weeks of age.
92. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times.
93. The method of clause 92, any other suitable clause, or any combination of suitable clauses, wherein the first administration is performed when the animal is about 12 weeks of age and the second administration is performed when the animal is about 16 weeks of age.
94. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed during molting of the animal.
95. The method of clause 94, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times.
96. The method of clause 94, any other suitable clause, or any combination of suitable clauses, wherein the administration is performed on the animal two or more times, wherein the second administration is performed about 4 weeks after the first administration.
97. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is between about 0.1 ml to about 1 ml.
98. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.10 ml.
99. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.25 ml.
100. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.50 ml.
101. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 0.75 ml.
102. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine is about 1 ml.
103. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x 1010 TCC.
104. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 106 TCC.
105. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 107 TCC.
106. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 108 TCC.
107. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 109 TCC.
108. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of about 1 x 1010 TCC.
109. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x 10lu TCC.
110. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 106 TCC.
111. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 107 TCC.
112. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky’ antigen at a dose of about 1 x 108 TCC.
113. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 109 TCC.
114. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of about 1 x 1010 TCC.
115. The method of clause 75, any other suitable clause, or any combination of suitable clauses, wherein the method further comprises administration of a second veterinary composition.
116. The method of clause 115, any other suitable clause, or any combination of suitable clauses, wherein the second veterinary composition is a second vaccine.
1 17. The method of clause 116, any other suitable clause, or any combination of suitable clauses, wherein the second vaccine comprises a Salmonella Enteritidis bacterin.
EXAMPLE 1
Method of Making Water-in-Oil Vaccine
The instant example describes an exemplary method for making a vaccine of the present disclosure. This example provides an exemplary method for making a water-in-oil vaccine.
An oil phase was prepared by combining mineral oil and Span 80 and then mixing the combination for at least 10 minutes using a magnetic stir bar. The resultant oil phase was then filter sterilized under aseptic conditions.
An aqueous phase was prepared by combining buffered saline, 40% Tween, formalin, an inactivated Salmonella typhimurium antigen, and is an inactivated Salmonella kentucky antigen. This combination was mixed for at least 5 minutes using a magnetic stir bar.
The oil phase and the aqueous phase were then emulsified. The oil phase was transferred into a Kady Mill mixing vessel. Mixing was initiated and then the aqueous phase was slowly added to the oil phase to create the emulsion. After at least 15 minutes of mixing, the emulsion was aseptically transferred into vials for later use as vaccine.
EXAMPLE 2
Vaccine Efficacy Analysis
In the instant example, the efficacy of vaccines of the present disclosure were evaluated. The exemplary vaccines used in the instant example were vaccines comprising an inactivated Salmonella typhimurium antigen and an inactivated Salmonella kentucky antigen.
Three different water-in-oil (W/O) vaccines were prepared with each vaccine comprising a different dosage of Salmonella typhimurium antigen and Salmonella kentucky antigen. The different doses included i) 1.0 x 108 tcc of Salmonella typhimurium antigen and 1.0 x 108 tcc of Salmonella kentucky antigen per dose; ii) 5.0 x 108 tcc of Salmonella
typhimurium antigen and 5.0 x 108 tcc of Salmonella kentucky antigen per dose; and iii) 1.0 x 109 tcc of Salmonella typhimurium antigen and 1.0 x 109 tcc of Salmonella kentucky antigen per dose. One water-in-oil-in-water (W/O/W) vaccine was prepared comprising 1.0 x 109 tcc of Salmonella typhimurium antigen and 1.0 x 109 tcc of Salmonella kentucky antigen per dose. A control W/O vaccine that did not comprise Salmonella typhimurium antigen or Salmonella kentucky antigen was also prepared.
For the instant example, 100 chickens were divided into five different treatment groups (i.e., 20 chickens per group). The five treatment groups are shown in Table 1: Table 1
The chickens in each treatment group were administered the vaccine twice (one administration at 12 weeks of age and a second administration at 16 weeks of age. Thereafter, the efficacy of vaccine in each treatment group was evaluated by challenging the chickens at 20 weeks of age with both Salmonella typhimurium and Salmonella kentucky.
Following the challenge, chickens were analyzed for “reisolation” of Salmonella typhimurium in intestine and in organs. Chickens observed to be negative for reisolation of Salmonella typhimurium were determined to be protected by the vaccine. Following the challenge, chickens were also analyzed for reisolation of Salmonella kentucky in intestine. Chickens observed to be negative for reisolation of Salmonella kentucky were determined to be protected by the vaccine.
Table 2 shows the results of vaccine efficacy following Salmonella typhimurium challenge. Table 2. Efficacy of Vaccine Following Salmonella typhimurium Challenge
- “A” = statistically significant difference over “B”
- “A” = statistically significant difference over “C”
- “B” = statistically significant difference over “C”
The instant example demonstrates that the exemplary vaccines were effective in providing cross-protection to chickens following a challenge with Salmonella typhimurium and Salmonella kentucky.
Claims
1. A composition comprising i) a first antigen and ii) a second antigen, wherein the first antigen is an inactivated Salmonella typhimurium antigen and wherein the second antigen is an inactivated Salmonella kentucky antigen.
2. The composition of claim 1, wherein the composition provides crossprotection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
3. The composition of claim 1, wherein the composition provides crossprotection against a Salmonella typhimurium infection and a Salmonella kentucky’ infection.
4. A vaccine comprising i) an effective amount of an inactivated Salmonella typhimurium antigen, ii) an effective amount of an inactivated Salmonella kentucky antigen, and an adjuvant.
5. The vaccine of claim 4, wherein the adjuvant is water-in-oil.
6. The vaccine of claim 4, further comprising a water-in-oil (W/O) component.
7. The vaccine of claim 4, wherein the adjuvant is water-in-oil-in-water.
8. The vaccine of claim 4, further comprising a water-in-oil-in-water (W/O/W) component.
9. The vaccine of claim 4, wherein the vaccine is configured as a multi-dose vial.
10. The vaccine of claim 4, wherein the vaccine provides cross-protection against a Salmonella infection caused by at least two of a Salmonella Group B bacterium, a Salmonella Group C bacterium, and a Salmonella Group D bacterium.
11. The vaccine of claim 4, wherein the vaccine provides cross-protection against a Salmonella typhimurium infection and a Salmonella kentucky infection.
12. A method of administering a vaccine to a non-human animal, said method comprising a step of administering to the animal an effective amount of the vaccine of any of claims 4-11.
13. The method of claim 12, wherein the method provides at least 85% efficacy against a Salmonella infection.
14. The method of claim 13, wherein the Salmonella infection is caused by a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof.
15. The method of claim 13, wherein the method provides at least 90% efficacy.
16. The method of claim 13, wherein the method provides at least 95% efficacy.
17. The method of claim 13, wherein the method provides efficacy in one or more organs of the non-human animal.
18. The method of claim 13, wherein the method provides efficacy in intestine of the non-human animal.
19. The method of claim 12, wherein the animal is an avian.
20. The method of claim 19, wherein the avian is selected from the group consisting of a chicken, a turkey, and a duck.
21. The method of claim 19, wherein the avian is a chicken.
22. The method of claim 21, wherein the chicken is a broiler chicken.
23. The method of claim 21, wherein the chicken is a layer chicken.
24. The method of claim 12, wherein the administration is a subcutaneous injection.
25. The method of claim 12, wherein the administration is an intramuscular injection.
26. The method of claim 12, wherein the administration is performed on the animal two or more times.
27. The method of claim 26, wherein the first administration is performed when the animal is about 12 weeks of age, and the second administration is performed when the animal is about 16 weeks of age.
28. The method of claim 12, wherein the administration is performed on the animal three or more times.
29. The method of claim 28, wherein the first administration is performed when the animal is about 12 weeks of age, the second administration is performed when the animal is about 16 weeks of age, and the third administration is performed when the animal is about 20 weeks of age.
30. The method of claim 12, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x 1010 TCC.
31. The method of claim 12, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x IO10 TCC.
32. The method of claim 12, wherein the method further comprises administration of a second veterinary composition.
33. The method of claim 32, wherein the second veterinary composition is a second vaccine.
34. The method of claim 33, wherein the second vaccine comprises a Salmonella Enteritidis bacterin.
35. A method of inducing an immune response in a non-human animal, said method comprising a step of administering to the animal an effective amount of a vaccine of any of claims 4-11.
36. The method of claim 35, wherein the immune response is against one or more of a Salmonella Group B bacterium, a Salmonella Group C bacterium, a Salmonella Group D bacterium, or any combination thereof.
37. The method of claim 35, wherein the immune response is against a Salmonella Group B bacterium.
38. The method of claim 35, wherein the immune response is against a Salmonella Group C bacterium.
39. The method of claim 35, wherein the immune response is against a Salmonella Group D bacterium.
40. The method of claim 35, wherein the immune response is against an inactivated Salmonella typhimurium antigen.
41. The method of claim 35, wherein the immune response is against an inactivated Salmonella kentucky antigen.
42. The method of claim 35, wherein the immune response comprises an immune response against an inactivated Salmonella typhimurium antigen and an immune response against an inactivated Salmonella kentucky antigen.
43. The method of claim 35, wherein the animal is an avian.
44. The method of claim 43, wherein the avian is selected from the group consisting of a chicken, a turkey, and a duck.
45. The method of claim 43, wherein the avian is a chicken.
46. The method of claim 45, wherein the chicken is a broiler chicken.
47. The method of claim 45, wherein the chicken is a layer chicken.
48. The method of claim 35, wherein the administration is a subcutaneous injection.
49. The method of claim 35, wherein the administration is an intramuscular injection.
50. The method of claim 35, wherein the administration is performed on the animal two or more times.
51. The method of claim 50, wherein the first administration is performed when the animal is about 12 weeks of age and the second administration is performed when the animal is about 16 weeks of age.
52. The method of claim 35, wherein the effective amount of the vaccine comprises an inactivated Salmonella typhimurium antigen at a dose of between about 1 x 106 and 1 x IO10 TCC.
53. The method of claim 35, wherein the effective amount of the vaccine comprises an inactivated Salmonella kentucky antigen at a dose of between about 1 x 106 and 1 x IO10 TCC.
54. The method of claim 35, wherein the method further comprises administration of a second veterinary composition.
55. The method of claim 54, wherein the second veterinary composition is a second vaccine.
56. The method of claim 55, wherein the second vaccine comprises a Salmonella Enteritidis bacterin.
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US20100247567A1 (en) * | 2007-04-19 | 2010-09-30 | Sotomayor Konky | Composition and method for controlling intestinal pathogenic organisms |
US20180339033A1 (en) * | 2013-08-24 | 2018-11-29 | Bharat Biotech International Limited | Methods for the Prevention of Salmonella Infections |
US10772954B2 (en) * | 2014-06-16 | 2020-09-15 | Biomune Company | Dual adjuvant vaccine compositions, preparation and uses |
WO2021021778A1 (en) * | 2019-07-30 | 2021-02-04 | Phibro Animal Health Corporation | A composition for mucosal administration to avians |
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US20100247567A1 (en) * | 2007-04-19 | 2010-09-30 | Sotomayor Konky | Composition and method for controlling intestinal pathogenic organisms |
US20180339033A1 (en) * | 2013-08-24 | 2018-11-29 | Bharat Biotech International Limited | Methods for the Prevention of Salmonella Infections |
US10772954B2 (en) * | 2014-06-16 | 2020-09-15 | Biomune Company | Dual adjuvant vaccine compositions, preparation and uses |
WO2021021778A1 (en) * | 2019-07-30 | 2021-02-04 | Phibro Animal Health Corporation | A composition for mucosal administration to avians |
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