The following table includes the leading candidates, however a number of these are not yet ready for a phase-1 trial but may be coming into trial over the next three to six months, and some are slightly longer term.
|Vaccine||Manufacturers (developers):||Vaccine details:||Testing timeline:|
|ChAd3-ZEBOV||GlaxoSmithKline (National Institutes of Health (NIH)||Chimpanzee adenovirus type-3 vector||In phase-1 trials; phase-3 trials are planned for December 2014 or January 2015|
|rVSV-Ebov||Newlink Genetics (the Public Health Agency of Canada) [Note, Merck is now co-developing this vaccine]||Weakened version of vesicular stomatitis virus (VSV) vector||Phase-1 trials beginning; hoped to be ready for phase-3 trials alongside ChAd3-ZEBOV in December or January|
|Ad26, Ad35, MVA ebola vaccine candidates||Johnson & Johnson and Bavarian Nordic||Human adenoviruses 26 and 35, and MVA in heterologous prime-boost approach||Phase-1 trials to start at the beginning of 2015|
|Recombinant protein – Ebola glycoprotein||Protein Sciences||Based on technology licensed as FluBlok influenza vaccine. Baculovirus-expressed recombinant protein||Clinical trials in first trimester of 2015|
|EBOV GP Vaccine||Novavax||Recombinant nanoparticle with proprietary adjuvant Matrix-M||Clinical trials to start during December 2014|
|Oral Ad5||VaxArt||Oral human adenovirus-based Ebola candidate (tablet vaccine)||Trials to start during first quarter of 2015|
|rVSV-EBOV||Profectus||Second VSV-based vaccine, has different deletions in VSV backbone than Newlink Genetic’s vaccine||Phase-1 trials in mid-2015. Note: Clinical data already available from this VSV expressing HIV gag protein|
|DNA-EBOV with electroporation||Inovio||DNA Ebola vaccine candidate||Clinical trials during 2015|
|Recombinant rabies EBOV||Thomas Jefferson University (NIH)||Recombinant rabies virus||Clinical testing to begin during 2015|
|Russian-made vaccines||Little information available: Developers include Vector and researchers from St. Petersburg||Three vaccines: Adenoviral technology, Lentivirus technology, and; An inactivated strain of the influenza virus||WHO actively requesting details|
Two candidate vaccines currently under clinical evaluation
There are two candidate vaccines where clinical trials are already underway (in safety dose finding studies).
One of these is a recombinant chimpanzee adenovirus-3 vaccine (ChAd3-ZEBOV) using a non-replicating virus, and the other is a recombinant vesicular stomatitis virus vaccine using a replicating virus (rVSV-Ebov). To target these vaccines to Ebola, the rVSV vaccine inserts the Ebola virus glycoprotein, while the ChAd3 virus vaccine ZEBOV has two inserts from the Ebola virus glycoprotein gene. Both of these were selected on the basis of stringent evidence of efficacy in non-human primate models, conferring a 100% protection following a post-lethal challenge.
In a study of animals given the ChAd3-ZEBOV vaccine, 16 were protected by a single dose of the vaccine and this same backbone has been used for a number of other diseases in many countries in Africa. Over 1300 people have received a vaccine using recombinant chimpanzee adenovirus-3 platform.
One issue regarding the rVSV-Ebov virus vaccine is that it is unknown exactly how this virus will replicate in humans, particularly in people with weak immune systems. Too little growth could make a weak vaccine, while too much could cause illness. The consequences of spreading rVSV-EVD to unvaccinated people or animals are unknown. One laboratory worker was given the vaccine after a needle-stick injury, and remained well. This does not prove that the vaccine will be safe or protective.
A large number of phase I studies looking at safety and dose selection in healthy volunteers are already underway.
ChAd3: Overview of Phase-1 trials
Site Number Trial start Characteristics
VRC – USA 20 September, 2014 Bivalent, healthy adults, dose-escalation, safety
Oxford – UK 60 September, 2014 Monovalent, healthy adults, dose-escalation, safety
CVD – Mali 40 October, 2014 Monovalent, healthy adults, dose-escalation, safety”
Gambia 40 Pending Monovalent, healthy adults, dose-selection, safety
Lausanne, 100 October, 2014 Monovalent, healthy adults, dose-selection, safety
Total vaccinated, Phase-1 = 260
rVSV: Overview of Phase-1 trials
Site Number Trial start Characteristics
WRAIR – USA 30 October, 2014 Healthy adults, dose-escalation, safety
NIAID – USA 30 October, 2014 Healthy adults, safety, two-dose schedule
Hamburg Germany 20 10 November, 14 Healthy adults, dose-selection, safety
Lambarene Gabon 60 10 November, 14 Healthy adults, dose-selection, safety
Kilifi, Kenya 40 10 November, 14 Healthy adults, dose-selection, safety
Geneva, 100 10 November, 14 Healthy adults, dose-selection, safety
Total vaccinated Phase-1 = >250
The key milestones for the vaccines program have been the initiation of phase-1 trials in November while, at the same time, developing protocols including for phase-3 trials across the different sites and including the affected countries. The hope is that by the middle of December 2014, there will be initial safety and immunogenicity data from phase-1 trials, and that shortly afterwards very large-scale phase-3 trials in Liberia can be undertaken.
If all goes according to plan with the early results on vaccine efficacy by April 2015, it may be possible to use these vaccines in the field if it is still necessary.
* Note: Since these data were presented by Dr Roth, preliminary safety data have been positive on the ChAd3-ZEBOV vaccine, while the Newlink and Merck vaccine had a temporary setback, after some patients complained of joint pain. However, trials of the vaccine are expected to start-up again soon.
Global Health Strategies generously supported Theo Smart’s attendance at the 63rd Annual American Society of Tropical Medicine and Hygiene Conference in New Orleans.