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Novel adenovirus

Pending Publication Date: 2021-03-04
GLAXOSMITHKLINE BIOLOGICALS SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a recombinant adenovirus that can be used as a medicament to treat mycobacterial infections, such as tuberculosis. The recombinant adenovirus contains a polynucleotide or polypeptide that encodes a mycobacterial antigen. This recombinant adenovirus can effectively stimulate an immune response against mycobacterial infections. The patent also describes a composition comprising the recombinant adenovirus and a pharmaceutically acceptable excipient.

Problems solved by technology

It is a major disease in developing countries, as well as an increasing problem in developed areas of the world.

Method used

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  • Novel adenovirus
  • Novel adenovirus
  • Novel adenovirus

Examples

Experimental program
Comparison scheme
Effect test

example 1

of ChAd155

[0417]Wild type chimpanzee adenovirus type 155 (ChAd155) was isolated from a healthy young chimpanzee housed at the New Iberia Research Center facility (New Iberia Research Center; The University of Louisiana at Lafayette) using standard procedures as described in Colloca et al. (2012) and WO2010086189, which is hereby incorporated by reference for the purpose of describing adenoviral isolation and characterization techniques

example 2

ector Construction

[0418]The ChAd155 viral genome was then cloned in a plasmid or in a BAC vector and subsequently modified (FIG. 2) to carry the following modifications in different regions of the ChAd155 viral genome:

[0419]a) deletion of the E1 region (from bp 449 to bp 3529) of the viral genome;

[0420]b) deletion of the E4 region (from bp 34731 to bp 37449) of the viral genome;

[0421]c) insertion of the F4orf6 derived from human Ad5.

[0422]2.1: Deletion of E1 Region: Construction of BAC / ChAd155 ΔE1_TetO hCMV RpsL-Kana #1375

[0423]The ChAd155 viral genome was cloned into a BAC vector by homologous recombination in E. coli strain BJ5183 electroporation competent cells (Stratagene catalog no. 2000154) co-transformed with ChAd155 viral DNA and Subgroup C BAC Shuttle (#1365). As shown in the schematic of FIG. 3, the Subgroup C Shuttle is a BAC vector derived from pBeloBAC11 (GenBank U51113, NEB) and which is dedicated to the cloning of ChAd belonging to species C and therefore contains the...

example 3

oduction

[0452]The productivity of ChAd155 was evaluated in comparison to ChAd3 and PanAd3 in the Procell 92 cell line.

[0453]3.1: Production of Vectors Comprising an HIV Gag Transgene

[0454]Vectors expressing the HIV Gag protein were prepared as described above (ChAd155 / GAG) or previously (ChAd3 / GAG Colloca et al, Sci. Transl. Med. (2012) 4:115ra). ChAd3 / GAG and ChAd155 / GAG were rescued and amplified in Procell 92 unto passages 3 (P3); P3 lysates were used to infect 2 T75 flasks of Procell 92 cultivated in monolayer with each vector. A multiplicity of infection (MOI) of 100 vp / cell was used for both infection experiments. The infected cells were harvested when full CPE was evident (72 hours post-infection) and pooled; the viruses were released from the infected cells by 3 cycles of freeze / thaw (−70° / 37° C.) then the lysate was clarified by centrifugation. The clarified lysates were quantified by Quantitative PCR Analysis with primers and probe complementary to the CMV promoter region....

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Abstract

There is provided adenoviral vectors encoding a mycobacterial antigen derived from a chimp adenovirus, and to related aspects.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This is a Continuation of U.S. patent application Ser. No. 15 / 747,545, filed Jan. 25, 2018, which is the U.S. National Stage application submitted under 35 U.S.C. § 371 for International Application No. PCT / EP2016 / 067621, filed Jul. 25, 2016, which claims priority to Application No. GB 1513176.6, filed Jul. 27, 2015 all of which are incorporated herein by reference in their entireties.SUBMISSION OF SEQUENCE LISTING ON ASCII TEXT FILE[0002]The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: VB65845AC1_US_Seq_Listing.txt; created 4 Aug. 2020; size: 437,640 bytes).FIELD OF THE INVENTION[0003]The present invention relates to adenoviral vectors encoding a mycobacterial antigen, more particular to adenoviral vectors derived from chimp adenovirus ChAd155, and to related aspects.BACKGROUND OF THE INVENTION[0004]Tuberculos...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/04C12N15/86A61K39/12C12N7/00A61P31/06A61K35/761C07K14/005C07K14/35A61K9/00A61K39/39A61K45/00C12N15/85
CPCA61K39/04C12N15/86A61K39/12C12N7/00A61P31/06A61K35/761A61K2039/545C07K14/35A61K9/0019A61K39/39A61K45/05C12N15/85C12N2710/10321C07K14/005C12N2710/10341A61K2039/5256C12N2740/16234C12N2760/18534A61K39/235C12N2710/10343
Inventor COLLOCA, STEFANOAMMENDOLA, VIRGINIAGRAZIOLI, FABIANAVITELLI, ALESSANDRANICOSIA, ALFREDOCORTESE, RICCARDO
Owner GLAXOSMITHKLINE BIOLOGICALS SA
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