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Notification report


Full notification file


General information

Notification Number
B/BE/20/BVW2

Member State to which the notification was sent
Belgium

Date of acknowledgement from the Member State Competent Authority
20/02/2020

Title of the Project
A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a modified Chimpanzee Adenovirus (ChAdOx1)-vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-vectored Multigenotype hrHPV Vaccine in Women with Low-grade HPV-related Cervical Lesions

Proposed period of release:
08/06/2020 to 31/03/2021

Name of the Institute(s) or Company(ies)
Vaccitech Limited, Schroedinger Building
Oxford Science Park,
Heatley Road
Oxford OX4 4GE;


3. Is the same GMO release planned elsewhere in the Community?
No

Has the same GMO been notified elsewhere by the same notifier?
No

GMO characterization

GMO is a:
DNA Virus

Identity of the GMO:
ChAdOx1-HPV
ChAdOx1-HPV is a recombinant replication-incompetent simian (chimpanzee-derived) adenoviral vector derived from serotype Y25, encoding 59 gene segments from HPV proteins E1, E2, E4, E5, E6 and E7 from genotypes 16, 18, 31, 52, 53 and 58; the segments are joined end-to-end and the resulting insert is a transgene of 4082 base pairs encoding a fusion protein of 1255 amino acids.
Adenoviruses are classified by the EMA as non-integrating. The ChAdOx1 vaccine vector was derived from the ChAdY25 after it was genetically modified and incapacitated for replication, by deletion of the essential E1 genes (Dicks, 2012); the non-essential E3 gene is also deleted. The genetically modified ChAdOx1 parent viral vector for ChAdOx1-HPV is not capable of genetic integration into the host. The adenoviral DNA will only replicate in permissive cells which provide the essential viral replication E1 region in trans e.g. Human Embryonic Kidney 293 (HEK293) cells (with which there are only short overlapping sequences, making the likelihood of recombination very low). ChAdOx1-HPV is a non-integrative virus and following infection of the target human host cell, ChAdOx1-HPV DNA localises in the cell nucleus but does not integrate its DNA into the host cell genome. Integration of adenovirus DNA into the host cell genome has been observed only as an extremely rare event in some human primary cell line cultures. It remains transiently episomal until the cell is destroyed.
The HPV transgene is a synthetic antigen sequence derived from consensus regions, not related to pathogenicity, from thousands of strains of HPV.


MVA-HPV
Orthopoxviruses are non-integrating. The MVA vaccine vector was derived from the replication-competent dermal vaccinia strain Chorioallantois Vaccinia virus Ankara (CVA) and has been attenuated by more than 570 serial passages in primary cultured Chicken Embryo Fibroblasts (CEF). These mutations have rendered the MVA virus highly attenuated and unable to productively replicate in most mammalian cell lines, including primary human cells and most transformed human cell lines. MVA is a non-integrative virus, following infection of the target human host cell, it remains exclusively in the cytoplasm, therefore, its DNA remains outside the cell nucleus eliminating any risk of integration of the viral DNA into the host genome.
The HPV transgene is a synthetic antigen sequence derived from consensus regions, not related to pathogenicity, from thousands of strains of HPV.


Information relating to the recipient or parental organisms from wich the GMO is derived
Common NameGenusSpeciesSubspeciesStrainPathovar
ChAdY25MastadenovirusSimian adenovirussubgroup CSerotype Y25-
CVAOrthopoxvirusvaccinia virus-Chorioallantois Vaccinia virus Ankara-

European Commission administrative information

Consent given by the Member State Competent Authority:
Not known