Efficacy testing of the rVSV-ZEBOV Ebola vaccine in Guinea Gunnstein Norheim MScPharm PhD Norwegian Institute of Public Health Member of Study Steering Group ESCAIDE November 13th 2015
Apr 12, 2017
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)