Efficacy testing of the rVSV-ZEBOV Ebola vaccine in Guinea, Dr. Gunnstein Norheim
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Transcript of Efficacy testing of the rVSV-ZEBOV Ebola vaccine in Guinea, Dr. Gunnstein Norheim
Efficacy testing of the rVSV-ZEBOV Ebola vaccine in Guinea
Gunnstein NorheimMScPharm PhD
Norwegian Institute of Public HealthMember of Study Steering Group
ESCAIDE November 13th 2015
Challenges for testing vaccine efficacy in epidemics-Ethical aspects and community engagement-Study designs for efficacy testing-Race against the clock
Foto: Daniel Berehulak, The New York Times
Setting and purpose of the Guinea vaccine trial
• Limitation of classical tools to stop outbreak
• Potential of vaccines to limit the outbreak• Provide complementary data to trials in Sierra
Leone (stepped wedge) and Liberia (RCT)
Menu of challenges in November 2014
• Study design• Study location• Implementation in Guinea• Choice of vaccine• Ethical and regulatory approval pathways• Community engagement• Financing
Study design: ring vaccination study
50% of rings randomized to immediate vaccination
Time (days)Compare incidence
50% of rings randomized to delayed vaccination
Frontline-workers study
• 1200 frontline workers• Immunogenicity• Adverse events
• Samples drawn at days 0, 7, 28, 84 and 180 after vaccination
• Samples to be analysed in US, Germany, UK and Norway
• Capacity building in Guinea
Major vaccine target: glycoprotein (GP)
Konstantinov et al. Visual Science 2011
Immunity against Ebola
Human natural immunityVaccine-induced immunityin non human primates
Becquart et al PLOSOne 2010:5:e9126Sullivan et al. Nature Reviews Microbiology 2009;7:393-400
Structures of Ebola Vaccine Candidates rVSV (Panel A) and cAd3 (Panel B).
Two vaccine candidates fulfilled requirements
Kanapathipillai R et al, NEJM Dec 11, 2014. CDC 1981. Graham Beards.
1. 100% protection in non-human primates (NHP)2. GMP product available
rVSV vaccine
chAd3 vaccine
Choice of study area: case variability and labs
Conakry: 85 beds
Gueckedou: 85 beds
Macenta: 60 beds (transfer)
Nzerekore: 40 beds
WHO situation report 10.12.2014
The process leading to the trial
• Protocol development, consent, SOPs• Ethics approvals: Norway, WHO and Guinea• Regulatory approval in Guinea• Monitoring for GCP adherence• Logistics, organisation• Data management: University of Bern
Logistics, organisation and data management
Photo: Sean Hawkey
Community engagement
Photos: Sean Hawkey
Vaccination of contacts
Frontline workers study
Photo: MSF
Interim results for 90 rings per 20th July 2015
Henao-Restrepo et al. Lancet July 31st 2015 WHO, August 9th 2015
Each ring visited at days 0, 3, 14, 21, 42, 63, and 84 post-vaccinationto document the potential occurrence of any serious adverse events
Comparability of rings
Interim results for 90 rings per 20th July 2015
Vaccine efficacy: 100%95% confidence interval: 74.7 – 100%
Immediate: 48 rings2014 vaccinated of 4123 contacts/cc
0 Ebola viral disease cases
Delayed: 42 rings1498 vaccinated of 3528 contacts/cc
16 Ebola viral disease cases
Henao-Restrepo et al. Lancet July 31st 2015
No new cases of Ebola virus disease were diagnosed in vaccinees from 6 days post-vaccination
• Request from MoH, August 2015
• Declared free of EVD transmission on 7th Nov.
Extension of trial to Sierra Leone
Latest developments in Guinea
• Ring vaccination trial continues• 4 new cases last 21d (Nov 7th). 0 cases last week• 69 contacts followed, completes 21d Nov 14th
WHO Ebola Situation report per 7th November 2015
The Guinea Trial: race against the clock
90 rings
www.cdc.gov
5th Nov 2014Country group formed
Vaccinationinitiated
Reached 90 rings
Last randomized ring
9 months
Publication 31st July 2015
5 months?
Lessons learned• Broad and open collaboration key to success• Clear leadership: «command and control»• Peer-review: study design, vaccine choice• Expertise diversity, pragmatism and speed• Community engagement, local study team
Photos: Sean Hawkey
Partners and funders
Chair, Study steering group: John-Arne Røttingen, NIPHRegulatory sponsor representative: Marie-Paule Kieny, WHOPrincipal investigators: Mandy K. Konde, Moussa Doumbia, Aboubacar Soumah
Funding• Wellcome Trust• Research Council of Norway• Institute Development
Research Centre, Canada• WHO• Medecins Sans Frontieres
Republic of Guinea: Sakoba Kéïta, Mandy Kader KondéWHO: Marie-Paule Kieny, Ana Maria Henao-Restrepo, Godwin Enwere, Souleymane Kone, Ximena Riveros, Andrea Vicari University of Florida: Ira M Longini, Natalie E DeanLSTHM: W John Edmunds, Anton Camacho, Conall H WatsonUniversity of Bern: Matthias Egger, Stefanie Hossmann, Sven TrelleEMLab: Miles W Carroll, Sophie Duraffour, Eeva Kuisma, Stephan GuntherCVD Mali: Moussa Doumbia, Myron M LevineMSF/Epicentre: Bertrand Draguez, Aboubacar Soumah, Rebecca GraisPHE: Sema MandalNIPH: John-Arne Røttingen, Gunnstein Norheim, Bjørg D. Nilsson, Sara Watle
The future
• Licensing and access to rVSV vaccine
• Identify a correlate of protection
• Develop a pan-Ebola vaccine
Choice of dose level – rVSV-ZEBOV vaccine
Huttner et al, Lancet Oct 2015
n=51 received rVSV-ZEBOV 5x105
n=35 received rVSV-ZEBOV 1x107
n=16 received rVSV-ZEBOV 5x107
n=13 received placebo (saline)
IgG against GP protein Neutralisation (pseudovirion)