WO2015138471A1 - Heat inactivated poxvirus improves vaccination results - Google Patents

Heat inactivated poxvirus improves vaccination results Download PDF

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Publication number
WO2015138471A1
WO2015138471A1 PCT/US2015/019736 US2015019736W WO2015138471A1 WO 2015138471 A1 WO2015138471 A1 WO 2015138471A1 US 2015019736 W US2015019736 W US 2015019736W WO 2015138471 A1 WO2015138471 A1 WO 2015138471A1
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WO
WIPO (PCT)
Prior art keywords
vaccine
heat
inactivated
poxvirus
vaccinia virus
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2015/019736
Other languages
French (fr)
Inventor
Bertram Jacobs
Trung Huynh
Negin BLATTMAN
Keith DUMBELL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arizona State University ASU
Arizona State University Downtown Phoenix campus
Original Assignee
Arizona State University ASU
Arizona State University Downtown Phoenix campus
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Arizona State University ASU, Arizona State University Downtown Phoenix campus filed Critical Arizona State University ASU
Priority to US15/125,024 priority Critical patent/US20170021009A1/en
Publication of WO2015138471A1 publication Critical patent/WO2015138471A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K39/12—Viral antigens
    • A61K39/275—Poxviridae, e.g. avipoxvirus
    • A61K39/285—Vaccinia virus or variola virus
    • 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
    • A61K39/12—Viral antigens
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5252—Virus inactivated (killed)
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5256—Virus expressing foreign proteins
    • 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
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/24011—Poxviridae
    • C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
    • C12N2710/24134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/24011—Poxviridae
    • C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
    • C12N2710/24161—Methods of inactivation or attenuation

Definitions

  • This application relates to the field of vaccination against infectious disease and more specifically to the use of heat- inactivated poxvirus in vaccines.
  • Active immunization involves administration of vaccines containing antigenic molecules (or genes for these molecules) derived from infectious agents. Vaccinated animals react with acquired immune responses and develop prolonged immunity to those agents. When properly used, vaccines are highly effective in controlling infectious diseases.
  • Vaccines may contain either living or killed organisms or purified antigens from these organisms. Vaccines containing living organisms tend to trigger the best protective responses. Killed organisms or purified antigens may be less immunogenic than living ones. As a result, vaccines that contain killed organisms or purified antigens usually require the use of adjuvants to maximize their effectiveness. Adjuvants may, however, cause local inflammation, and multiple doses or high doses of antigen increase the risks of producing hypersensitivity reactions.
  • Vaccinia virus was and is still being used as a live-virus vaccine against smallpox virus, which is genetically related to vaccinia.
  • a vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals, but it may cause a mild rash and fever.
  • compositions including a heat- inactivated poxvirus, such as vaccinia virus, that induces one or more interferons, a potent antiviral and immune stimulator.
  • a heat- inactivated poxvirus such as vaccinia virus
  • vaccinia virus that induces one or more interferons
  • a potent antiviral and immune stimulator a potent antiviral and immune stimulator.
  • Mixing heat inactivated vaccinia virus with live, virulent vaccinia virus protects animals from lethal infection and still allows induction of a protective immune response.
  • This disclosure further relates to methods of vaccine preparation and
  • vaccinia virus administration including a heat- inactivated poxvirus, such as vaccinia virus.
  • Embodiments described herein relate to compositions including heat-inactivated poxvirus, e.g., vaccinia virus, and to methods of preparation and administration of same.
  • heat-inactivated poxvirus e.g., vaccinia virus
  • Vaccinia virus contains within its genome several proteins that give the virus resistance to interferons.
  • K3L is a protein with homology to the protein eukaryotic initiation factor 2 (eIF-2alpha). K3L protein inhibits the action of PKR, an activator of interferons.
  • E3L is another protein encoded by Vaccinia. E3L also inhibits PKR activation.
  • heat inactivated poxvirus e.g., vaccinia virus
  • a live, virulent virus such that a recipient such as an animal or human is both protected from lethal infection and produces a protective immune response.
  • heat inactivation of vaccinia virus allows it to induce interferon, a potent antiviral and immune stimulator.
  • a vaccine composition could be a mixture of heat inactivated vaccinia virus and one or more of live vaccine vectors or nonreplicating vaccine components.
  • killed or inactivated pathogens do not replicate, they typically cannot revert to a more virulent form capable of causing disease.
  • inactivated pathogens tend to provide a shorter length of protection than live vaccines, and are more likely to require boosters to create long-term immunity.
  • heat-inactivated poxvirus has been discovered to confer better immunogenecity.
  • the poxvirus may be heat inactivated by one of several known means.
  • the virus may inactivated by dry heat at 95 °C for 2 hours or by moist heat at 60 °C for 10 hours.
  • a vaccination dosage is based on known dosages for poxvirus, such as vaccinia virus (e.g., prophylaxis vaccination for small pox).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Compositions including a heat-inactivated poxvirus, such as vaccinia virus, that induces one or more interferons in a vaccine recipient. The compositions may further include one or more live vaccine vectors and non-replicating vaccine components. Methods of vaccine preparation and administration including a heat-inactivated poxvirus, such as vaccinia virus, improve vaccine immunogenicity and safety.

Description

HEAT INACTIVATED POXVIRUS IMPROVES VACCINATION RESULTS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application No.
61/950,494 filed on March 10, 2014.
FIELD OF THE INVENTION
[0002] This application relates to the field of vaccination against infectious disease and more specifically to the use of heat- inactivated poxvirus in vaccines.
BACKGROUND OF THE INVENTION
[0003] Active immunization involves administration of vaccines containing antigenic molecules (or genes for these molecules) derived from infectious agents. Vaccinated animals react with acquired immune responses and develop prolonged immunity to those agents. When properly used, vaccines are highly effective in controlling infectious diseases.
[0004] Vaccines may contain either living or killed organisms or purified antigens from these organisms. Vaccines containing living organisms tend to trigger the best protective responses. Killed organisms or purified antigens may be less immunogenic than living ones. As a result, vaccines that contain killed organisms or purified antigens usually require the use of adjuvants to maximize their effectiveness. Adjuvants may, however, cause local inflammation, and multiple doses or high doses of antigen increase the risks of producing hypersensitivity reactions.
[0005] Vaccinia virus was and is still being used as a live-virus vaccine against smallpox virus, which is genetically related to vaccinia. A vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals, but it may cause a mild rash and fever.
Moreover, certain complications and/or vaccine adverse effects occasionally arise. The chance of this happening is significantly increased in people who are immunocompromised. SUMMARY OF THE INVENTION
[0006] This disclosure relates to compositions including a heat- inactivated poxvirus, such as vaccinia virus, that induces one or more interferons, a potent antiviral and immune stimulator. Mixing heat inactivated vaccinia virus with live, virulent vaccinia virus protects animals from lethal infection and still allows induction of a protective immune response.
[0007] This disclosure further relates to methods of vaccine preparation and
administration including a heat- inactivated poxvirus, such as vaccinia virus.
[0008] These and other aspects of the invention will be apparent upon reference to the following detailed description and figure. All references cited throughout are hereby incorporated by reference herein.
DETAILED DESCRIPTION OF THE INVENTION
[0009] Embodiments described herein relate to compositions including heat-inactivated poxvirus, e.g., vaccinia virus, and to methods of preparation and administration of same.
[0010] Vaccinia virus contains within its genome several proteins that give the virus resistance to interferons. For example, K3L is a protein with homology to the protein eukaryotic initiation factor 2 (eIF-2alpha). K3L protein inhibits the action of PKR, an activator of interferons. E3L is another protein encoded by Vaccinia. E3L also inhibits PKR activation.
[0011] Thus in one novel aspect, it has been discovered that heat-inactivation of a poxvirus allows it to induce interferon, a potent antiviral and immune stimulator, and thereby produce an improved vaccination response in a vaccinated subject.
[0012] In another embodiment, heat inactivated poxvirus (e.g., vaccinia virus) is mixed with one or more of a live, virulent virus such that a recipient such as an animal or human is both protected from lethal infection and produces a protective immune response. [0013] In a more specific embodiment, it has been discovered that heat inactivation of vaccinia virus allows it to induce interferon, a potent antiviral and immune stimulator. Moreover, a vaccine composition could be a mixture of heat inactivated vaccinia virus and one or more of live vaccine vectors or nonreplicating vaccine components.
[0014] Because killed or inactivated pathogens do not replicate, they typically cannot revert to a more virulent form capable of causing disease. However, inactivated pathogens tend to provide a shorter length of protection than live vaccines, and are more likely to require boosters to create long-term immunity. However, heat-inactivated poxvirus has been discovered to confer better immunogenecity.
[0015] The poxvirus may be heat inactivated by one of several known means. For example, the virus may inactivated by dry heat at 95 °C for 2 hours or by moist heat at 60 °C for 10 hours. Moreover, a vaccination dosage is based on known dosages for poxvirus, such as vaccinia virus (e.g., prophylaxis vaccination for small pox).
[0016] In view of the above, the advantages of the embodiments herein over current technology are increased safety of live vaccine vectors and increased immunogenicity.
[0017] The claims are not intended to be limited to the embodiments and examples described herein.

Claims

What is claimed is:
1. A vaccine composition including a heat- inactivated p o x v i rus.
2. The vaccine composition of claim 1, wherein said vaccine composition induces interferon in a recipient upon administration of said vaccine composition.
3. The vaccine composition of claim 1, wherein said heat- inactivated poxvirus comprises a vaccinia virus.
4. The vaccine composition of claim 2, wherein said heat-inactivated poxvirus comprises a vaccinia virus.
5. The vaccine composition of claim 1, further comprising a mixture of said heat- inactivated poxvirus and one or more of a live vaccine vector and a non-replicating vaccine component.
6 . The vaccine composition of claim 5, wherein said heat-inactivated poxvirus comprises a vaccinia virus.
7 . A method for preparation of a vaccine, comprising the step of adding a heat- inactivated poxvirus to said vaccine prior to administration to a vaccine recipient.
8. The method of claim 7, wherein said heat- inactivated poxvirus comprises vaccinia virus.
9. The method of claim 7, further comprising adding one or more of a live vaccine vector and a non-replicating vaccine component to said vaccine.
10. A vaccination method, comprising administering a vaccine composition including a heat- inactivated p o x v i rus to an animal or human.
1 1. The vaccination method of claim 10, wherein said heat-inactivated poxvirus comprises a vaccinia virus.
12. The vaccination method of claim 10, further comprising a mixture of said heat- inactivated poxvirus and one or more of a live vaccine vector and a non-replicating vaccine component.
PCT/US2015/019736 2014-03-10 2015-03-10 Heat inactivated poxvirus improves vaccination results Ceased WO2015138471A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/125,024 US20170021009A1 (en) 2014-03-10 2015-03-10 Heat Inactivated Poxvirus Improves Vaccination Results

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461950494P 2014-03-10 2014-03-10
US61/950,494 2014-03-10

Publications (1)

Publication Number Publication Date
WO2015138471A1 true WO2015138471A1 (en) 2015-09-17

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WO (1) WO2015138471A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115300622A (en) 2015-02-25 2022-11-08 纪念斯隆-凯特琳癌症中心 Use of inactivated modified vaccinia virus ankara as a sole immunotherapy of solid tumors or in combination with immune checkpoint blockers
CN107847534B (en) 2015-04-17 2022-10-04 纪念斯隆凯特琳癌症中心 Use of MVA or MVA delta E3L as an immunotherapeutic agent against solid tumors
IL261321B2 (en) 2016-02-25 2023-12-01 Memorial Sloan Kettering Cancer Center Recombinant MVA or MVADELE3L expressing human FLT3L and their use as immunotherapeutic agents against solid tumors
KR20180133395A (en) 2016-02-25 2018-12-14 메모리얼 슬로안 케터링 캔서 센터 Replicable attenuated vaccinia virus with or without the expression of human FLT3L or GM-CSF and for which the thymidine kinase has been deleted for cancer immunotherapy
WO2018209315A1 (en) 2017-05-12 2018-11-15 Memorial Sloan Kettering Cancer Center Vaccinia virus mutants useful for cancer immunotherapy
MX2021003013A (en) 2018-09-15 2021-08-11 Memorial Sloan Kettering Cancer Center Recombinant poxviruses for cancer immunotherapy.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030092145A1 (en) * 2000-08-24 2003-05-15 Vic Jira Viral vaccine composition, process, and methods of use
US20040018193A1 (en) * 2002-03-29 2004-01-29 Ken Alibek Rapid-acting broad spectrum protection against biological threat agents

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1263936T3 (en) * 2000-03-14 2006-02-13 Bavarian Nordic As second strain of the modified Vacciniavirus Ankara (MVA)

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030092145A1 (en) * 2000-08-24 2003-05-15 Vic Jira Viral vaccine composition, process, and methods of use
US20040018193A1 (en) * 2002-03-29 2004-01-29 Ken Alibek Rapid-acting broad spectrum protection against biological threat agents

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