A polynucleotide herpes virus vaccine

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/38 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C07K 14/035 (2006.01)

Patent

CA 2267645

Genes encoding herpes simplex virus type 2 (HSV-2) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. In a DNA titration, it was found that a single immunization of 0.5 µg of (one) PNV, gave 90 % seroconversion by ten weeks post immunization. Immune antisera neutralized both HSV-2 and HSV-1 in cell culture. When animals were challenged with HSV-2, significant (p.001) protection from lethal infection was achieved following PNV vaccination. DNA constructs may be full-length, truncated and/or mutated forms and may be delivered along or in combination in order to optimize immunization and protection from HSV infection.

On a cloné des gènes codant des protéines de type 2 du virus d'herpès simplex (HSV-2) dans des vecteurs d'expression eucaryote afin d'exprimer les protéines codées dans des cellules de muscles de mammifères in vivo. On a immunisé ces animaux par injection de ces produits de recombinaison d'ADN, désignés vaccins de polynucléotides ou PNV, dans leurs muscles. On a découvert, dans un titrage d'ADN, qu'une seule immunisation de 0,5 µg d'un PNV, produisait ?90 % de séroconversion sur dix semaines de post-immunisation. Des antisérums immuns ont neutralisé à la fois HSV-2 et HSV-1 dans des cultures de cellules. Quand on a testé HSV-2 sur des animaux, on a obtenu une protection importante (p?0.001) contre l'infection mortelle en utilisant la vaccination de PNV. Ces produits de recombinaison d'ADN peuvent être des formes de longueur totale, tronquées ou ayant subi une mutation et peuvent être administrés seuls ou combinés, de manière à optimiser l'immunisation et la protection contre l'infection par HSV.

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