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Compositions and methods

A technology of composition and medicine, applied in the field of adenovirus vector

Pending Publication Date: 2021-08-06
OXFORD UNIV INNOVATION LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, reviewers identified Shingrix's 2-dose dosing and its tolerability profile as potential weaknesses

Method used

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  • Compositions and methods
  • Compositions and methods
  • Compositions and methods

Examples

Experimental program
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example 1

[0315] Example 1 - Viral vector vaccine against VZV

[0316] We have generated a viral vector vaccine against VZV.

[0317] Our data show that the vaccine of the present invention is superior to the currently licensed prior art Zoster vaccine ( figure 1 ).

[0318] The higher CMI routinely achieved with viral vector vaccines may translate into higher efficacy compared with other vaccine modalities, and advantageously, viral vector vaccines require only Effectiveness is obtained with a single injection.

[0319] we refer to figure 1 .

[0320] Use 11x 10 7 IU ChAdO X1 -VZVgpE or 1x 10 7 IU ChAdO X2- VZVgpE or 1.3x10 3 Balb / c mice in each group were inoculated intramuscularly with pfu Zotax (n=5). Splenocytes were harvested 2 weeks after final vaccination and cellular immune responses to peptides spanning the entire glycoprotein E were measured by ELISpot analysis.

[0321] ChAdO X1 - Response after VZV-gE was significantly higher than that after vaccination with Z...

example 2

[0349] Example 2: Effective expression of vectors of the present invention

[0350] We show western blot analysis of viral vector expression of VZVgpE. Subconfluent HEK293T (ChAdO X1 ). After 18 hours the cells were harvested, lysed, and the protein supernatant lysates were electrophoresed on a Biorad 4-12% gradient gel and probed with abcam 52549VZV diluted 1:1000 in 0.05% PBST to detect expression with ECL reagents .

[0351] The result is as Figure 7 shown. The swimlanes are as follows:

[0352] 0-molecular marker

[0353] 1 – ChAdO on HEK293T X1 VZVgpE MOI 1

[0354] 2 – ChAdO on HEK293T X1 VZVgpE MOI 5

[0355] 3 – ChAdO on HEK293T X2 VZVgpE MOI 1

[0356] 4 – ChAdO on HEK293T X2 VZVgpE MOI 5

[0357] 5 – VZV+ve control ~ 100ng

[0358] 6 – VZV+ve control ~ 500ng

[0359] It was thus demonstrated that the composition of the invention produces antigen expression in human cells.

example 3

[0360] Example 3: Immunogenicity of Viral Vectors Encoding Varicella-Zoster Virus Glycoprotein E

[0361] We demonstrate the cellular immunogenicity of a single-injection vaccine against VZV.

[0362] we refer to Figure 8 a. Use 11x 10 7 IU ChAdO X1 -VZVgpE or 1x 10 7 IU ChAdO X2 -VZVgpE or 1.3x 10 3 Balb / c mice in each group were inoculated intramuscularly with pfu Zotax (n=5). Splenocytes were harvested 2 weeks after final vaccination and cellular immune responses to peptides spanning the entire glycoprotein E were measured by ELISpot analysis.

[0363] we refer to Figure 8 b. Use 1x 10 7 IU X1 -VZVgpE ("old mice" are pre-breeding mice, usually older than 24 weeks) or 1.3x 10 3 Groups of Balb / c mice (n=5, usually 8-10 weeks old unless otherwise stated) were inoculated intramuscularly with pfu Zotax. Splenocytes were harvested at indicated times after final vaccination and cellular immune responses against peptides spanning the entire glycoprotein E were measur...

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Abstract

The invention relates to a viral vector comprising nucleic acid having a polynucleotide sequence encoding at least one epitope of the varicella-zoster virus (VZV)GlyE antigen, wherein the viral vector is an adenoviral vector. The invention also relates to uses, compositions for use in medical treatments, and methods of medical treatment.

Description

technical field [0001] The present invention relates to compositions useful for inducing an immune response against Varicella-Zoster Virus (VZV). In particular, the present invention relates to viral vectors comprising epitopes of the VZV Gly E protein, such as adenoviral vectors comprising the same. Background technique [0002] Varicella-zoster virus (VZV or "shingles virus") causes chickenpox primarily in children. But, more importantly, the same virus can re-emerge in adults, often decades after primary varicella infection, causing severe shingles disease. [0003] Herpes zoster (shingles, or herpes zoster), is an infection of the nerve and the skin around it. According to NHS estimates, about one in four people will have at least one episode of shingles in their lifetime. [0004] The main symptoms of shingles are pain, followed by a rash that develops into itchy blisters that resemble chickenpox in appearance. New blisters may appear for up to a week, but after a f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/25A61K38/16C07K14/04C12N15/861
CPCA61K39/25C07K14/04C12N15/861A61K38/00A61P31/22A61P37/02C12N15/86C12N2710/10043A61K35/761
Inventor S·C·吉尔伯特S·塞巴斯蒂安A·V·S·希尔T·拉姆
Owner OXFORD UNIV INNOVATION LTD
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