August 29, 2014

expert reaction to treatment of monkeys with ZMapp

Eighteen rhesus macaques infected with Ebola were given the drug ZMapp, with  100% recovery rate, reported a study in Nature.

Prof Peter Piot, Director of the London School of Hygiene & Tropical Medicine and Professor of Global Health, said:

“This well designed trial in non-human primates provides the most convincing evidence to date that ZMapp may be an effective treatment of Ebola infection in humans. It is now critical that human trials start as soon as possible.

“The resurgence of Ebola serves as a reminder of the importance of investing in health systems and infrastructure. This terrible disease is controllable with proper hygiene practices which all too often are not in place. We must work to find ways to alleviate symptoms and save lives with new treatments but at the same time we must act to prevent the spread of the disease.

“I never thought that 40 years after I encountered the first Ebola outbreak, this disease would still be taking lives on such a devastating scale.”

Prof Jonathan Ball, Professor of Molecular Virology at the University of Nottingham, said:

“The degree of protection offered by the new cocktails is impressive to say the least, especially considering that they worked after the animals developed outward signs of infection.

“Whether or not these impressive results translate into humans infected with a different strain of the virus remains to be seen – only a few treatments have been used so far in humans, and not everyone receiving Zmapp survived.

“Despite these promising results, this treatment won’t stop the current outbreak.  With estimates that as many as 20,000 people might get infected there’s simply not enough of the stuff to go round.

“Infection prevention and control will win the day and there needs to be far more international effort than we’re seeing at the moment.”

Prof Tim Morris, School of Veterinary Medicine and Science at the University of Nottingham, and co-editor of Nonhuman Primates in Biomedical Research, said:

“The focus of the current Ebola outbreak in West Africa has rightly been on the human population, but the virus also has a deadly effect on local non-human primate populations, including chimpanzees, gorillas and other monkeys.  The research published today by a team from Canada, China and the USA builds on earlier work in monkeys and tests the positive response to novel antibody treatment both immediately infection is seen, but also when treatment has been delayed.

“For proven treatments to be available, for a disease such as Ebola which affects many parts of the body, this research provides a stark context for the needs, and challenge, of using a clearly representative animal model, and in particular non-human primates; with the undoubted harm to the animals to be weighed against the clear benefits to humans from understanding if delayed treatment still works. At present whilst there seems no complete substitute to some animal use in this serious situation, the work does illustrate the ongoing use of the 3R’s ‘alternatives’ in animal research; with replacement of the early antibodies produced in live animals with production in plants, the reduction in non-human primate use by initial testing in cultures and guinea pigs, and the listed refinements in animal care.”

Dr Alain Kohl, MRC Programme Leader, MRC/University of Glasgow Centre for Virus Research, said:

“The experiments in rhesus monkeys are very interesting because they demonstrate for the first time that ZMapp can act against Ebola virus, and at different times post exposure. What needs to be done next is assess against how many strains and species of the virus it can act. Clinical trials in humans are not possible so some questions will go unanswered. At present too few people have received the drug to allow conclusions about efficacy and treatment timings, though in emergency situations it is at least one potentially useful option.”

Prof Roger Lemon, University College London Institute of Neurology, said:

“This underlines the special nature of non-human primate models and their importance for human health. Clearly UK animal research regulations must continue to allow research involving these models.”

Prof David J. Evans, Professor of Virology at the University of Warwick, said:

“The recent manuscript from Kobinger and colleagues addresses two of the most important unanswered questions about the efficacy of ZMapp, a novel therapy for Ebola virus infections. In studies in non-human primates they demonstrate that ZMapp, an optimised antibody cocktail of three humanized antibodies produced in tobacco plants, provides complete post-exposure protection to recipient animals up to eleven days after virus challenge, even when the animals are exhibiting advanced symptoms of disease.

“In their studies, all animals survived and had undetectable viral loads 21 days post-infection. This is an extremely encouraging result for a virus which has an incubation period of 2-21 days in humans and for which no vaccine exists.

“Secondly, they demonstrate that the antibodies are reactive – at least in the assays used – with the Guinean isolate of Ebola currently circulating in West Africa. This is an important confirmatory result since the antibodies were generated against the related Zairerian isolate of the virus.

“These results do not prove that the healthcare workers who received ZMapp and recovered did so due to the therapy. Others who also received ZMapp succumbed to the virus. Distinguishing between correlation and causation will require analysis of the clinical data on viral loads before and after therapy was administered. Nevertheless, the results are encouraging.

“Widespread availability and use of ZMapp will require human safety testing and licensing, coupled with scale-up of the manufacturing process. These are time-consuming and expensive phases of getting a therapy from the laboratory to the clinic. Whether this can be achieved to curtail the current epidemic remains to be determined. In the meantime, quarantine, palliative care and barrier methods to prevent transmission must remain a priority.”

Prof Martin Hibberd, Professor of Emerging Infectious Disease at the London School of Hygiene & Tropical Medicine, said:

“This looks to be a very well designed study with better than expected results, which give great hope for future clinical trials. I hope the team can receive sufficient funding to undertake these clinical trials straight away as this is by far the most advanced potential treatment option available to my knowledge. The paper does not describe how long the monoclonal antibodies persist, but other similar antibodies are known to persist for weeks, which also opens the possibility of using this treatment prophylactically, such as protecting front line health care workers. ”

‘Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp’ by Xiangguo Qiu et al  published in Nature on Friday 29 August 2014. 

Declared interests

None declared