As the fear of the Ebola epidemic grips the world, with the virus finding its way to countries outside of the African continent, scientists are working to develop efficient diagnostic tests as well as preventive and curative measures to defeat the virus that has overwhelmed West Africa.
A company in the United Kingdom, Primerdesign Ltd, has worked on a diagnostic test with a quick turnaround that detects the viral nucleotide sequence—a trait that would render the test highly sensitive, allowing for early-stage diagnosis. The process involves isolating viral RNA from the patient’s blood sample followed by quantitative PCR. The company is set to meet with officials at the World Health Organization (WHO) to make the kit available at the disease forefront in Africa.1,2
This test would work whether or not the patient was exhibiting symptoms. If put into widespread use, such a diagnostic tool could identify those who have contracted the virus before they become ill, providing a window of opportunity for these patients to be quarantined.
A perspective published online in the New England Journal of Medicine documented that there are 2 candidate vaccines currently being considered by WHO:
• cAd3-EBOV (cAd3), developed by GlaxoSmithKline (GSK) and the US National Institute of Allergy and Infectious Diseases (NIAID)
° Phase 1 studies initiated in the United States and the United Kingdom
° Preclinical studies in primates demonstrated 100% efficacy • rVSVΔG-EBOV-GP (rVSV), developed by NewLink Genetics and the Public Health Agency of Canada
° Trial enrollment to start soon
° Preclinical studies in primates demonstrated 100% efficacy.3
Being dose-response studies, the preliminary phase 1 trials of these vaccines are not expected to provide efficacy data. The cAd3 vaccine is being evaluated in bivalent (Zaire strain of the
virus; responsible for the current epidemic) and monovalent (Sudan strain of the virus) forms, with preliminary results on immunogenicity and safety expected in November. With trials set to
begin soon for rVSV in the United States, the Canadian government has donated 800 vials of the vaccine to WHO.3
A meeting in Geneva end of September—convened by the WHO—brought together scientists, public health officials, and individuals from the industry and regulatory agencies (including from the FDA and the European Medicines Agency), who emphasized the need to expedite phase 1 trials and share the resulting data. This would allow forfaster initiation of phase 2 trials. Phase 2a trials are proposed to be conducted in Africa outside the infection zone, and would be conducted in parallel with phase 2b trials in exposed populations. All participants in the trials are to receive the vaccine at some point in the trial, to ensure access to healthcare workers exposed to patients in clinics and hospitals, family members of patients, and people who cleanse and bury deceased patients. A follow-up meeting is planned for November, when preliminary results from the phase 1 trials will be available, to decide the future course of action.3'
So far, ZMapp and TKM-Ebola are the only experimental treatments against the virus. A combination of 3 monoclonal antibodies being developed by Mapp Biopharmaceutical Inc, ZMapp has not undergone human trials,4 but has been administered in a handful of patients. Of these, a Spanish nurse who was infected with the virus5 and 2 American aid workers infected in Liberia, survived. A Spanish priest and a Liberian doctor did not.6 However, according to the CDC, very few courses of ZMapp were manufactured, and the available doses have all been depleted.4
The company is working to accelerate production of this biological regimen.
TKM-Ebola, the alternative, is a viral RNAi molecule being developed by a Canadian company Tekmira Pharmaceuticals. In addition to a fast-track designation by the FDA, TKM-Ebola is being developed under the “animal rule” guidelines, which accept well-controlled animal experiments as sufficient evidence to allow marketing of a drug product.7