Codon-optimized polynucleotide-based vaccines against human...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/38 (2006.01) A61K 39/245 (2006.01) A61P 31/20 (2006.01) C12N 15/11 (2006.01) C12N 15/62 (2006.01) C07K 14/02 (2006.01)

Patent

CA 2508228

The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

L'invention concerne des vaccins à base de cytomégalovirus à base de polynucléotides. Elle concerne notamment des plasmides codant de manière fonctionnelle les antigènes DE HCMV, dans lesquels les régions de codage naturelles des antigènes DE HCMV ont été modifiées de manière à assurer une traduction améliorée dans les cellules humaines ou d'autres cellules mammaliennes grâce à l'optimisation du codon. Les antigènes DE HCMV, dont il est question dans l'invention, comprennent de façon non limitée pp65, la glycoprotéine B (gB), IE1, ainsi que des fragments, variants ou dérivés de ces antigènes. Dans certains modes de réalisation, des séquences ont été supprimées, par exemple, la kinase présumée Arg435-Lys438 dans pp65 et l'ancrage de membrane ainsi que les domaines endocellulaires dans gB. L'invention concerne aussi des procédés destinés à induire une réponse immune à HCMV chez un mammifère tel qu'un humain, qui consistent à administrer un plasmide codant un antigène de HCMV à codon optimisé, qui est décrit ci-dessus. L'invention concerne aussi des compositions pharmaceutiques comprenant des plasmides codant un antigène de HCMV à codon optimisé décrit ci-dessus ainsi que des adjuvants, des excipients ou des modulateurs immuns.

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