A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 39/245 (2006.01) A61K 39/25 (2006.01) A61K 39/255 (2006.01) A61K 39/265 (2006.01) A61K 39/27 (2006.01) C07K 14/04 (2006.01) C12N 7/04 (2006.01)
Patent
CA 2571261
Viruses having weakened ability to establish and/or maintain latency and their use as live vaccines are described. The vaccines have one or more alterations in genes that provide continued virus replication but that inhibit latency. The vaccine materials and methods for their construction are exemplified with the varicella zoster virus. Deletion of a significant portion from both copies of the varicella zoster gene ORF63 was shown to inhibit establishment of a latent infection from a live vaccine form of the virus. Insertion of an additional ORF62 gene which is partially truncated with the ORF63 deletion inhibited establishment of latency and allowed normal growth of the virus. Other desirable viral antigen encoding sequence(s) and/or cytokine genes advantageously may replace deleted genetic material to enhance a desired immunological response. Aspects of the discovery pertain to live vaccines of other viruses, and can provide a variety of vaccines having greater safety.
L'invention porte sur des virus à capacité affaiblie de production et/ou de maintien de latence, et sur leur utilisation comme vaccins vivants. Lesdits vaccins comportent une ou plusieurs altérations de leurs gènes permettant la poursuite de la réplication mais inhibant la latence. On donnera comme exemple les matériaux et les méthodes de construction du virus zostérien de la varicelle. La suppression d'une partie significative de deux copies du gène zostérien ORF63 de la varicelle a montré qu'elle inhibait la survenue d'une infection due à la forme vivante du vaccin par le virus. L'insertion d'un gène additionnel ORF62 partiellement tronqué et la suppression du gène ORF63 ont inhibé la survenue de la latence tout en permettant la croissance normale du virus. D'autres séquences désirables codant pour l'antigène viral et/ou des gènes de cytokines peuvent remplacer avantageusement le matériau génétique supprimé afin d'obtenir la réponse immunologique souhaitée. D'autres aspects de la découverte portent sur des vaccins vivants d'autres virus pouvant constituer une série de vaccins très sûrs.
Cohen Jeffrey I.
Cox Edward M. Jr.
Pesnicak Lesley M.
Departmen T. Of Health And Human Services The United States Of America As Represented By The Secretary
Robic
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