Treatment and vaccines for Ebola virus disease
In absence of vaccines to protect against Ebola virus disease (EVD) or specific drug for treatment in 2014, potential new Ebola therapies and vaccines were reviewed during four WHO meetings organised with relevant stakeholders from early September 2014 onwards. Following advice from WHO, several clinical trials assessing efficacy of convalescent whole blood, plasma, antiviral drugs and vaccines have been initiated.
In the European Union, the European Medicines Agency EMA reviewed available information on Ebola treatments and vaccines currently under development in order to support fast-track authorisation. The use of whole blood or plasma from EVD survivors does not require an EU authorisation and is the responsibility of National Competent Authorities for Blood and Blood Components.
Several antivirals drugs and protocol of treatment using convalescent whole blood or plasma have been proposed for treatment with very limited data on potential efficiency. Often several therapeutic approaches have been combined, and some trials have been halted due to limited efficiency. Detailed information about the treatment trials conducted in West Africa is presently limited . Data from trials will require a detailed analysis prior providing some recommendations in addition to supportive treatment. Funding for basic research on EVD specific treatment continues. The use of convalescent plasma as a treatment against EVD appears to be safe and feasible. Data about efficacy are presently under analysis .
Several experimental vaccines have been proposed for trials . Phase 1 trial investigates the safety and immune response of the vaccine on a small number of healthy individuals, phase 2 trial determines the optimal dose of vaccine to achieve protection safely and phase 3 trial investigates the ability of the vaccine to protect against the disease. Several vaccine candidates are under trials .
The most advanced candidate vaccine rVSV –ZEBOV has been tested in phase 1 and 2 trials in Germany, Switzerland, Gabon and Kenya with the goal of assessing immunogenicity and safety. Some limited side effects have been reported but immunogenicity after a single dose and safety have been considered satisfactory [3-5].
In Guinea, a phase 3 trial has been launched on 7 March 2015 to test the rVSV-EBOV vaccine for efficacy and effectiveness to prevent Ebola (“Ebola ça suffit” clinical trial)  .One objective was to assess if the vaccine protects the contacts who are vaccinated and if vaccinating the contacts creates a ring of protected individuals around the index case to prevent further spread of the infection.
Preliminary data showed very encouraging results according to an independent committee that monitors the study [6,7]. The trial have shown that the rVSV-ZEBOV vaccine is able to protect immunized individuals (after a delay of about 10 days). None of the 2 014 contacts of Ebola patients who were vaccinated immediately after exposure developed disease more than 10 days after vaccination. Sixteen of the 2 380 persons in the contact group who were vaccinated three weeks after exposure, developed the disease. Vaccination has been now proposed to all contacts of EBO cases including children more than 5 years-old and pregnant women. Similar ring vaccination has been extended to Sierra Leone in September 2015. An ancillary study regarding Ebola front-line workers is extended to expand the amount of information available on the safety of the vaccine rVSV-ZEBOV.
Phase 2/3 trials have been initiated in West Africa for some other candidate vaccines following encouraging results in phase 1 trial but limited information is presently available [8-11].
It is unlikely that vaccine efficacy data will be available before a fast-track authorization of the vaccines by regulatory agencies.
Vaccines will have undergone limited testing in humans, and post-authorization monitoring of safety and effectiveness will be important.
The WHO Director General has initiated a Strategic Advisory Group of Experts (SAGE) Working Group on Ebola Vaccines and Vaccination. SAGE has been asked to give its Ebola vaccine recommendations based on the best available scientific evidence and public health policy but the final decision on offering vaccines in West Africa lies with the Ministries of Health in each of the affected countries.
WHO provides a complete panorama of the treatments, vaccines and ongoing trials that can be consulted using the following links:
- WHO - News on vaccines, therapies, diagnostics
- WHO - Ebola vaccines, therapies, and diagnostics Questions and Answers
- WHO - Q&A on trial of Ebola Virus Disease vaccine in Guinea
1. Jacobs M, Aarons E, Bhagani S, Buchanan R, Cropley I, Hopkins S, et al. Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. Lancet Infect Dis. 2015 Aug 25.
2. World Health Organization. Ebola vaccines, therapies, and diagnostics Geneva: WHO; 2015 [cited 2015 October 12].
3. Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe - Preliminary Report. N Engl J Med. 2015 Apr 1.
4. Huttner A, Dayer JA, Yerly S, Combescure C, Auderset F, Desmeules J, et al. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2015 Aug 3.
5. Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Munoz P, et al. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine - Preliminary Report. N Engl J Med. 2015 Apr 1.
6. Ebola ca Suffit Ring Vaccination Trial Consortium The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola. BMJ. 2015;351:h3740.
7. Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015 Aug 29;386(9996):857-66.
8. Zhu FC, Hou LH, Li JX, Wu SP, Liu P, Zhang GR, et al. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet. 2015 Jun 6;385(9984):2272-9.
9. Rampling T, Ewer K, Bowyer G, Wright D, Imoukhuede EB, Payne R, et al. A Monovalent Chimpanzee Adenovirus Ebola Vaccine - Preliminary Report. N Engl J Med. 2015 Jan 28.
10. Tapia MD, Sow SO, Lyke KE, Haidara FC, Diallo F, Doumbia M, et al. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial. The Lancet Infectious Diseases.
11. Mennechet FJ, Tran TT, Eichholz K, van de Perre P, Kremer EJ. Ebola virus vaccine: benefit and risks of adenovirus-based vectors. Expert Rev Vaccines. 2015 Sep 1:1-8.