Respiratory syncytial viruses expressing immune modulatory...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/86 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07K 14/14 (2006.01) C07K 14/54 (2006.01) C12N 7/04 (2006.01) C12N 15/62 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2379362

Recombinant respiratory syncytial virus (RSV) are provided which express one or more immune modulatory molecules. The recombinant virus is modified by addition or substitution of a polynucleotide sequence encoding the immune modulatory molecule, which is preferably a cytokine. Introduction of the cytokine increase, decrease, or otherwise enhances aspects of viral biology and/or host immune responses to RSV to facilitate vaccine use of the virus. Cytokines for use within the invention include but are not limited to interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), or interleukin 18 (IL-18), tumor necrosis factor (TNF) alpha, interferon gamma (IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF). The polynucleotide or immune modulatory molecule is preferably added or substituted into the recombinant viral genome or antigenome, typically at an intergenic or other non-coding site, as a separate gene but may be otherwise expressed, for example as a fusion protein.

L'invention concerne des virus syncytiaux respiratoires recombinés (RSV) qui expriment une ou plusieurs molécules modulatrices immunitaires. Le virus recombiné est modifié par l'ajout ou par la substitution d'une séquence polynucléotidique codant pour la molécule modulatrice immunitaire, qui est de préférence une cytokine. L'introduction de la cytokine permet d'accroître, de diminuer ou d'améliorer autrement des aspects de la biologie virale et/ou les réponses immunitaires d'hôte à RSV, et facilite ainsi l'utilisation vaccinale du virus. Les cytokines s'utilisant dans l'invention comprennent notamment, mais pas exclusivement, l'interleukine 2 (IL-2), l'interleukine 4 (IL-4), l'interleukine 5 (IL-5), l'interleukine 6 (IL-6) ou l'interleukine 18 (IL-18), le facteur de nécrose des tumeurs (TNF) alpha, l'interféron gamma (IFN) et le facteur de stimulation des colonies de granulocytes-macrophages (GM-CSF). Le polynucléotide ou la molécule modulatrice immunitaire est de préférence ajouté(e) ou substitué(e) dans le génome ou l'antigénome viral recombiné, généralement à un site intergénique ou à une autre site non codant, comme gène séparé, mais peut être exprimé autrement, par exemple comme protéine de fusion.

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