Rapid therapy development through Open nCoronavirus Vaccine Platform

Informations projet

OPENCORONA

N° de convention de subvention: 101003666

DOI

10.3030/101003666

Projet clôturé

Date de signature de la CE 6 Avril 2020

Date de début 1 Avril 2020

Date de fin 31 Mars 2024

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 3 000 000,00

Contribution de l’UE

€ 3 000 000,00

Coordonné par

KAROLINSKA INSTITUTET
Sweden

CORDIS fournit des liens vers les livrables publics et les publications des projets HORIZON.

Les liens vers les livrables et les publications des projets du 7e PC, ainsi que les liens vers certains types de résultats spécifiques tels que les jeux de données et les logiciels, sont récupérés dynamiquement sur OpenAIRE .

Livrables

Documents, reports (33)

Project risk management plan

This deliverable will outline the procedures for risk monitoring and evaluation throughout the project and include a risk register.

Evaluation of immunogenicity of all candidates

All vaccine candidates have been evaluated and if working, also tested for immunogenicity in mouse and rabbit studies. The samples have been analyzed.

Screening of sera from human vacinees by in vitro neutralization

Completed analysis of human sera obtained from the vaccinated healthy volunteers in the phase I clinical trial to neutralize SARS-COV-2 in cell culture.

Interim Activity Report

Delivery of Interim Activity report for Month 1-6

Synthesis of vaccine candidates, proteins and peptides

All vaccine candidates, proteins and produced and delivered to KI

Results from vaccine and challenge study

Completed analysis of protection studies in mice were immunized mice have been challenged with SARS-COV-2. This assists in the selection of the vaccine candidate.

Documentation for EMA

Provide complete documentation of the Cliniporator to the EMA/MPA for use in delivery of plasmid DNA vaccines in humans

GMP manufactured aseptically filled plasmid drug product

Dispensing of the vaccine candidate

QC tested and QP released GMP plasmid drug product

QC tested and QP released GMP produced vaccine candidate

Protocol for neutralization assay

Established assay for determination of neutralizing antibodies to SARS-COV-2 that can be used to test mouse and rabbit sera

Summarizing stability data report(s) for BDS

Report that describes the long term stability of the vaccine candidate

Selection of the best vaccine candidate for GMP and tox studies

One vaccine candidate has been selected based on safety and immunogenicity for production according to GMP and GLP toxicology testing.

Study plan for the GLP toxicity study

Written plan with the design of the toxocological study of the vaccine candidate

Manufactured GMP grade bulk drug substance pDNA

Production of a GMP grade bulk drug substance of the vaccine candidate

QC tested and QP released GMP drug substance

Release of a GMP produced vaccine candidate

A single step delivery procedure

Develop a device that is added to the Cliniporation electrode handle that enables injection of DNA and in vivo electroporation in a single step. This may or may not be used in the clinical trial depending on requirements from the EMA/MPA.

Communication and Dissemination Plan

Establish a Communication and Dissemination Plan

Optimization of selected vaccine candidates to further avoid a cytokine storm

ORF mutants of vaccine candidates that lost the ability to activate pro-inflammatory responses

Assays to measure cytokine induction and IFN supression

Primers, RT-qPCR assays, transfection protocols, control constructs, transfection protocols, reporter assays

Report writing for the IMPD, month

A written report of the toxicological evaluation of the vaccine candidate according to GLPto be submitted to EMAMPA

Midterm recruitment report
Approvals from ethics committee and EMA/MPA for phase I clinical trial
Completed clinical trial in humans and writing of report
Summarizing stability data report(s) for plasmid drug product

Written reports on the stability of the GMP produced vaccine candidate

Pre-Production Evaluation and plasmid production for toxicology studies

Complete study report on the manufacturing system performance and plasmid production for toxicological evaluation.

Consortium secured intranet and Management handbook

These tools will facilitate communication and establish the principles of work within the consortium. The Management Handbook will contain all internal consortium agreement related rules (for publication, etc.), key contact and info to use the intranet, plus a “digest” of H2020 rules easier to understand for SMEs and advices adapted to the consortium.

Manufactured and QP released Master Cell Bank

Generation of a Master cell bank for the vaccine and QP release

A locked Cliniporator with pulse pattern for plasmid DNA delivery

Establishment of a pulse pattern for in vivo electroporation that is optimized for delivery of plasmid DNA

Assessment of cytokine induction and IFN suppression by first set of vaccine candidates

Statistically robust data on upregulation of IFN-beta, IFN-lambda 1 and 2, IL-6, IL-8, TNF-alpha, CCL4, CCL5, CXCL10. Statistically robust data on dysregulation of IFN-beta induction or IFN signaling

Evaluation of the management tools and procedure

This document will outline the outcomes of the internal evaluation of the management tools and procedures put in place in OPENCORONA including recommendations for future improvements.

Completion of the GLP toxicity study, month

Completed toxicological evaluation according to GLP of the vaccine candidate

Optimization selected vaccine candidates to further avoid of suppression of IFN induction

ORF mutants of vaccine candidates that lost the ability to suppress IFN induction

Challenge protocol

Established protocol for infecting mice with SARS-COV-2 before or completed vaccinations

Websites, patent fillings, videos etc. (1)

Website

External Project Website launch.

Publications

Peer reviewed articles (5)

A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells

Auteurs: Sofia Appelberg Gustaf Ahlén Jingyi Yan Negin Nikouyan Sofie Weber Olivia Larsson Urban Höglund Soo Aleman Friedemann Weber Emma Perlhamre Johanna Apro Eva-Karin Gidlund Ola Tuvesson Simona Salati Matteo Cadossi Hanna Tegel Sophia Hober Lars Frelin Ali Mirazimi Matti Sällberg
Publié dans: EMBO Molecular Medicine, 2022, ISSN 1757-4684
Éditeur: EMBO Press
DOI: 10.15252/emmm.202215821

Inhibition of SARS–CoV-2 by type I and type III interferons

Auteurs: Ulrike Felgenhauer, Andreas Schoen, Hans Henrik Gad, Rune Hartmann, Andreas R. Schaubmar, Klaus Failing, Christian Drosten, Friedemann Weber
Publié dans: Journal of Biological Chemistry, Numéro 295/41, 2020, Page(s) 13958-13964, ISSN 0021-9258
Éditeur: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1074/jbc.ac120.013788

Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease

Auteurs: Jingyi Yan Chandrashekar Ravenna Bangalore Negin Nikouyan Sofia Appelberg Daniela Nacimento Silva Haidong Yao Anna Pasetto Friedemann Weber Sofie Weber Olivia Larsson Urban Höglund Gordana Bogdanovic Malin Grabbe Soo Aleman Laszlo Szekely Attila Szakos Ola Tuvesson Eva-Karin Gidlund Matteo Cadossi Simona Salati Matti Sällberg
Publié dans: Molecular Therapy, Numéro Volume 32, Numéro 2, 7 February 2024, 2024, Page(s) Pages 540-555, ISSN 1525-0016
Éditeur: Nature Publishing Group
DOI: 10.1016/j.ymthe.2024.01.007

The SARS-CoV-2 N Protein Is a Good Component in a Vaccine

Auteurs: Gustaf Ahlén, Lars Frelin, Negin Nikouyan, Friedemann Weber, Urban Höglund, Olivia Larsson, Marie Westman, Ola Tuvesson, Eva-karin Gidlund, Matteo Cadossi, Sofia Appelberg, Ali Mirazimi, Matti Sällberg
Publié dans: Journal of Virology, Numéro 94/18, 2020, ISSN 0022-538X
Éditeur: American Society for Microbiology
DOI: 10.1128/jvi.01279-20

Imaging of SARS-CoV-2 infected Vero E6 cells by helium ion microscopy

Auteurs: Natalie Frese, Patrick Schmerer, Martin Wortmann, Matthias Schürmann, Matthias König, Michael Westphal, Friedemann Weber, Holger Sudhoff, Armin Gölzhäuser
Publié dans: Beilstein Journal of Nanotechnology, Numéro 12, 2021, Page(s) 172-179, ISSN 2190-4286
Éditeur: Beilstein-Institut Zur Forderung der Chemischen Wissenschaften
DOI: 10.3762/bjnano.12.13