Modified Vaccinia virus Ankara for the vaccination of neonates

a technology of vaccinia virus and ankara, which is applied in the field of modified vaccinia virus ankara for the vaccination of neonates, to achieve the effects of increasing the activation level of factors, increasing the number of dendritic cells, and facilitating the initiation of vaccinia virus replication

Inactive Publication Date: 2006-06-15
BAVARIAN NORDIC AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0017] It is the object of the present invention to provide means to vaccinate newborn humans and animals, respectively, against foreign antigens and antigens that are associated with diseases in humans and animals, respectively. More particularly, it is the object of the present invention to provide means allowing the accelerated maturation of the immune system of newborn animals and humans. It is a further object of the present invention to provide means that allow vaccinating neonatal animals, including humans, against poxvirus infections, in particular against smallpox. DETAILED DESCRIPTION OF THE INVENTION
[0018] According to the present invention it was unexpectedly found that it is possible to safely and efficiently vaccinate and / or treat neonatal or prenatal animals, including humans, with viruses that are capable of infecting cells of the neonatal or prenatal animal, including a human, but not capable of being replicated in said cells to infectious progeny virus. In particular it has been shown that the viruses used according to the present invention, such as MVA, in particular MVA-BN and its derivatives (see below), can be administered to newborns without showing any harmful effects. The vaccination of the animal with the virus leads to a specific immune response against the virus used for vaccination and / or to a general vaccination against foreign antigens and tumour antigens as explained below in more detail. Moreover, the viruses used according to the present invention lead to an induction and / or enhancement of the maturation of the immune system, which is associated with an increase in the number of dendritic cells and factors such as Interferons. The vaccination with the viruses used according to the present invention is possible even if the formulation that is administered to the animal does not comprise an adjuvant.

Problems solved by technology

(ii) by a failure to replicate in a mouse strain that is incapable of producing mature B and T cells and as such is severely immune compromised and highly susceptible to a replicating virus, for administration to induce a general immune stimulation in an animal, including a human, in need thereof, such a

Method used

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  • Modified Vaccinia virus Ankara for the vaccination of neonates
  • Modified Vaccinia virus Ankara for the vaccination of neonates
  • Modified Vaccinia virus Ankara for the vaccination of neonates

Examples

Experimental program
Comparison scheme
Effect test

example 1

(I) MVA-BN and DISC-HSV induces DC of the CD11c+and CD8+phenotype in newborn animals

[0142] First set of experiments: Newborn mice are naturally immunodeficient because the IFN system is not mature. The number and activation state of DC, the best producers of IFN know today has not been analyzed. DC can be induced in vitro as well as in vivo by a variety of stimuli. In these studies it was tested whether a controlled MVA-BN replication could induce DC and analyzed their phenotype. Groups of mice were injected with 106 plaque forming units (p.f.u.) of MVA-BN or saline only within 1-2 days after birth and in some cases 5 days after birth. Blood and spleen cells from individual mice of both groups were analyzed by FACS and the data compared.

[0143] Data from 7 to 8 individual mice indicated that treatment with MVA-BN increased CD11c+cells 2-3 fold accompanied with increased expression of MHC II and increased presence of T cells of the CD4 or CD8 type Interestingly, CD19 / 54, a marker fo...

example 2

[0154] (i) MVA-BN treated neonatal mice survive a challenge with 100 to 500 LD50 of HSV-1

[0155] Groups of mice were treated with the standard dose of MVA-BN one or 2 days after birth and challenged at 7-8 days of age with 100 to 500 LD50 of Herpes simplex virus 1 (HSV-1) (FIG. 4). MVA BN treated mice survived the challenge with HSV 1, whereas all the control mice died within 5-6 days after inoculating the challenge virus.

[0156] To further support these observations, 9 challenge experiments were performed with 40 MVA BN treated and 45 control mice. More than 80 % of the virus treated mice survived the challenge, whereas all the control mice died (FIG. 5).

[0157] In a separate set of experiments the mice were treated at birth with MVA-BN (2.5×106 TCID50 mouse). At day 8 a challenge with either 103 (1 LD50) or 105 (100 LD50) PFU of HSV-1 was performed. Following MVA-BN vaccination 65% of the mice survived a viral dose that killed 100% of the control mice (100 LD50) and 90% survived a...

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Abstract

The invention concern the use of a virus for the preparation of a medicament for the vaccination or treatment of a neonatal or prenatal animal, including a human, wherein the virus is capable of infecting the cells of the neonatal or prenatal animal, including a human, but not capable of being replicated to infectious progeny virus in the neonatal or prenatal animal, including a human. The virus is preferably a Modified Vaccinia Virus Ankara. In particular, the invention concerns the vaccination of neonates against infections with viruses belonging to the same virus group than the virus used for vaccination. Moreover, the invention concerns the vaccination of neonates against antigens selected from foreign antigens and tumour antigens, wherein the tumour antigen and / or the foreign antigen are different from the antigens associated with the virus. The invention further concerns the use of viruses as defined above to increase the level of factors which activate dendritic cells or their precursor cells and / or to increase the number of dendritic cells or their precursor cells and / or to increase the production and / or cellular content of an interferon (IFN) or IL-12.

Description

[0001] The invention concern thes use of a virus for the preparation of a medicament for the vaccination or treatment of a neonatal or prenatal animal, including a human, wherein the virus is capable of infecting the cells of the neonatal or prenatal animal, including a human, but not capable of being replicated to infectious progeny virus in the neonatal or prenatal animal, including a human. The virus is preferably a Modified Vaccinia Virus Ankara. [0002] In particular, the invention concerns the vaccination of neonates against infections with viruses belonging to the same virus group than the virus used for vaccination. Moreover, the invention concerns the vaccination of neonates against antigens selected from foreign antigens and tumour antigens, wherein the tumour antigen and / or the foreign antigen are different from the antigens associated with the virus. The invention further concerns the use of viruses as defined above to increase the level of factors which activate dendriti...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C12P21/06A61K39/245A61K39/285A61K48/00C12N7/00C12N15/863
CPCA61K39/245A61K39/285A61K45/06A61K48/00A61K2039/5254A61K2039/55C12N7/00C12N15/86C12N2710/16643C12N2710/24143A61K39/12A61K2039/545C12N2710/24134
Inventor ACKERMANN, MATHIASSUTER, MARKHEFTI, HANS PETERFRANCHINI, MARCOVOLLSTEDT, SABINECHAPLIN, PAUL
Owner BAVARIAN NORDIC AS
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