MVA-SARS-2-S DZIF COVID-19 vaccine candidate
Marylyn M. Addo (UKE), Stephan Becker (UMR), Gerd Sutter (LMU), Andreas Neubert (IDT), Thomas Hesterkamp (PDU-DZIF) TTU/TI XYZ DrostenChristian Marylyn Addo DZIF DZIF - Emerging Infections Emerging Clinical TrialsClinical Infection Outbreak Virus Virus ecology medicine Antiviral Test platform surveillance ; diagnostics − − − DZIF African Partner Institutions Product ClinicalTrials Unit infrastructures ; Development Unit Development Public Public Epidemiology : Health BSL3/4 BSL3/4 Vaccinology Virology labs Gerd Sutter Gerd Stephan Becker TTU/TI XYZ Portrait of vacciniavirus MVA D. D. Electron Spehner micrograph / G. Sutter Sutter G. / Mayr & Munz Mayr& Munz Zentralbl Bakteriol Orig A1964 Stickl et al. al. et Dtsch Med Wochenschr 1974 TTU/TI XYZ Sutter Sutter MVA MVA • • • & non efficient experience Moss, Moss, - replicating as 1992, Sutter et al et Sutter 1992, production vector with virus various ., 1994 and in in for mammalian vector delivery gene vaccines of heterologous hosts expression in in , high level clinical antigens testing of biological and safety vaccination TTU/TI XYZ viruses Persistent Emerging viruses Emerging MVA MVA vectors Bacteria as candidate Parasites vaccines Allergies Tumors TTU/TI XYZ MVA - SARS - 2 - S: Design Design S: andpreclinical testing • • • • • • • Protective cells antibodiesT and Immunizationsinducemice spike in protein- substratecell growthcapacity in Full for manufacturing Genetic homogeneity,genetic identity, genetic stability Production of mature ~190 Expressionfull- of MVAplatform technology based on MVALMUF6 efficacy length SARSlength in in mice against kDa - CoV spike glycoprotein SARS - 2 S genesequence2 S - CoV specific specific - 2 infection TTU/TI XYZ − MVA follow Ankara Based • • • Koch T/Dahlke C etal.,2020 Volzal., A et 2015 Song F et al., 2013 on on the - vector - MERS validated MVA platform - MERS S recombinant - as blueprint blueprint as S , MVA , development - SARS Modified - 2 - S was was S vaccina designed virus to pharmaceutical and biotech biotech and pharmaceutical provided by IDT provided from global confidence in the services services the in confidence industry, and government
scientific research. scientific TTU/TI XYZ Worldwide Introduction to IDT IDT to Introduction Carsten Klocke Owner Holding GmbH GmbH Holding Klocke • • • • vaccines testClinicalmaterials for Rockville U.S.A. and productionBSL2 facilities development I EMA and FDA compliance, ANVISA ready and Stefan Quality controlanalysis Quality and Filling andfinishing II I to phases clinical Clinicaltest materialsfor Contract development Klocke Biologika (CEOs) (CEOs) • recombinant vaccines DevelopmentSite for Magdeburg, Germany development characterization and Process employees in 1,600 2019 Biologicals • • • • • • immunotherapeutic products Viral vaccines, Genetherapy Dessau Quality controlanalysis Quality and Packaging Filling andfinishing production Commercial Clinicaltest materialsfor clinicalphasesI to III Contract development turnover2018 in € 209 m € 209 - Rosslau , Germany and invested by IDTsince € 440 m € 440 1993 Further clinical development program MVA-SARS-2-S (Spike) Phase 1 Studie at UKE Study initiation 30.9.2020
Arrival of the vaccine UKE 1.10.2020
https://idt-biologika.de/ MVA vaccine plattform at DZIF
MVA: Viraler Vektor Nicht-replizierend gene of interest
MVA-(pathogen of interest)
DZIF clinical portfolio for MVA vaccines- all investigator-initiated trials (IIT):
MVA-MERS-S Middle East Respiratory Syndrome CoV • Phase Ia Studie: UKE, financing DZIF S1 S2 - completed. (Koch, Dahlke et al., 2020)
• Phase Ib/II Studien: CEPI-funded project - consortial partners DZIF, IDT, EMC & CR2O (Niederlande) S protein - Development program still ongoing - Phase 1b Start planned for end of 2020
SARS-CoV-2
MVA-SARS-2-S S1 S2 • Phase I Studie: financing DZIF (initiated 30.9.2020)
• Phase II/III Studien: BMBF-Förderung (IDT)
S protein Graphic: BioRender Clinical testing of a corona vaccine against MERS-CoV: MVA-MERS-S: Blueprint for MVA-SARS-S
1x107 PFU 1x108 PFU MVA-MERS-S
100% Seroconversion in HD Gruppe
The vaccine was well tolerated. Antibody and T-cell responses were generated. MVA-MERS-S showed robust immune responses & 100% seroconversion in the high dose group
ELISA Virus Neutralization
PRNT80
Koch, Dahlke et al., Lancet ID 2020 Now approved: Phase I study MVA-SARS-2-S (responsible as sponsor according to AMG: UKE)
Study design is almost identical to the Phase 1 vaccine study against MERS-CoV Phase I study initiation after approval by Ethics Committee (27.9) and PEI approval on 30.9.2020. First vaccinations planned for October 2020
An open-label, single-center Phase I trial to assess the safety, tolerability and immunogenicity of two ascending doses of Long-term collaboration for early clinical trials the candidate vaccine MVA-SARS-2-S with the Clinical Trial Center North.
Aims: Safety, tolerability and immunogenicity of the vaccine candidate MVA-SARS-2-S
Healthy adults(18-55 years)
1x107 IU 1x108 IU MVA-SARS-2-S MVA-SARS-2-S
Primary Objectives Evaluation of safety and tolerability of two intramuscular dose administrations and two ascending dose levels of MVA-SARS-2-S in healthy adults
Secondary Objectives to quantify binding antibodies against the SARS-CoV-2 spike protein and to evaluate seroconversion rates in healthy adults after two dose levels and two administrations of MVA-SARS-2-S Outlook: How does the current approval of the phase 1 study fit into the overall development program?
Phase I
Sponsor: UKE Multi-center study n=600 Q4/2020 1. Impfung Phase II Oktober 2020
Sponsor: Klinikum Phase III München Multi-center study N>20000 2021 Thanks to the team ! Back up slides MVA Impfstoffplattform
Frühere Studien • 1968-1985: MVA wurde als Impfstoff gegen Pocken verwendet MVA • Mehr als 120 000 Menschen wurde mit MVA geimpft • Es wurden keine schweren Nebenwirkungen beobachtet
Rekombinanter • Vektorimpfstoff MVA (gegen HIV, Tuberkulose, Ebola etc.) MVA • Mehr als 7500 Menschen mit einem rMVA geimpft • Mehr als 247 Studien registriert • Mehr als 1000 Menschen mit einem schwachen Immunsystem geimpft • Verträglichkeit in Kindern