Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B

A technology of measles virus and syncytial virus, applied in the direction of viruses, viral peptides, antiviral agents, etc.

Inactive Publication Date: 2001-05-09
WYETH HOLDINGS CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These secondary vaccination failures indicate limitations of existing vaccines in inducing and maintaining adequate and long-term antiviral protection (11, 12, 13)

Method used

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  • Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B
  • Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B
  • Mutations responsible for attenuation in measles virus or human respiratory syncytial virus subgroup B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] measles virus

[0184] Moraten MV vaccine virus was grown for one passage before preparing RNA for sequence analysis, directly from Attenuvax TMVaccine vials (Lot#0716B), allowing Schwarz vaccine virus to grow one generation (Lot96G04 / M179 G41D), while Zagreb and Rubeovax TM Vaccine viruses were grown in Vero cells for two passages each. MV wild-type isolate Montefiore (57) was passaged in Vero cells for 5-7 passages, and then the RNA material was extracted. Similarly, MV wild-type isolates 1977, 1983 (14) were grown for 5-5 years before extracting material for analysis. 7 generations. From J. The Edmonston wild-type isolate from Dr. Beeler (CBER) (see Figure 1) was received before the original isolate had been passaged 7 times in human kidney cells, 3 times in Vero cells, and then in Vero before being used for sequence analysis. A virus that is passed once in a cell.

[0185] RNA was prepared by infecting Vero cells at a multiplicity of infect...

Embodiment 2

[0202] RSV subgroup B

[0203] The temperature-sensitive (ts) phenotype is closely related to in vivo attenuation; in addition, some non-temperature-sensitive mutations may also be attenuating. Identification of temperature-sensitive and non-temperature-sensitive attenuated mutants was achieved by sequence analysis and assessment of the temperature-sensitive, cold-adapted (ca), and in vivo growth phenotypes of RSV mutants and revertants.

[0204] The genomes of the following three RSV 2B strains have been completely sequenced: the 2B wild-type parent, its ts and ca derivatives, designated 2B33F, and a ts(+) revertant, designated 2B33F TS(+). The 2B33F strain is described in US Patent No. 08 / 059,444(88), incorporated herein by reference. After identifying the mutation region in 2B33F, it was passaged in vitro at 39°C, and after passage in African green monkeys or chimpanzees, another nine 2B33F "reverted strains" were obtained, and their previously identif...

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Abstract

Isolated, recombinantly-generated, attenuated measles viruses and respiratory syncytial subgroup B viruses having defined attenuating mutations are described. Vaccines are formulated comprising such viruses and a physiologically acceptable carrier. The vaccines are used for immunizing an individual to induce protection against measles virus or respiratory syncytial subgroup B virus.

Description

field of invention [0001] The present invention relates to an isolated, recombinantly produced, attenuated measles virus or human respiratory syncytial virus subgroup B having specific attenuating mutations. This invention was made with government support and was made with funds provided by public health organizations. The government has certain rights in this invention. Background of the invention [0002] Enveloped, antisense single-stranded RNA viruses have unique organization and expression patterns. The genomic RNA of antisense single-stranded viruses serves two template functions in nucleocapsid composition: as a template for the synthesis of messenger RNA (mRNA) and as a template for the synthesis of the antigenomic (+) strand. Antisense single-stranded RNA viruses encode and package their own RNA-dependent RNA polymerase. Messenger RNA is only synthesized when the nucleocapsid enters the cytoplasm of infected cells. Viral replication occ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/165A61P31/12C12N15/09C07K14/12C07K14/135C12N7/04
CPCC12N2760/18422A61K2039/51C07K14/005C12N2760/18522A61P31/12C12N7/04
Inventor S·A·乌登M·S·西迪V·B·伦道夫D·A·博纳古里
Owner WYETH HOLDINGS CORP
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