Ebola virus vaccine developed to protect wild gorillas and chimpanzees

The current Ebola virus outbreak in Guinea, Sierra Leone and Liberia is a stark reminder on the need for effective therapies and vaccines for this disease, which has claimed the lives of thousands of people in West Africa in a series of outbreaks since the 1970’s.

It is not just the human inhabitants of West Africa who are threatened by the Ebola virus. Over the past few decades thousands of endangered gorillas and chimpanzees in the wild have been killed in devastating outbreaks, including over 5,000 gorillas in just one outbreak in Northern Congo in 2002—2003.

A new report (1) by scientists at the University of Cambridge and New Iberia Research Center illustrates “high conservation potential” of vaccines for endangered wild primates devastated by viral disease. The paper published today in the prestigious scientific journal PNAS shows that candidate vaccines which despite very promising preclinical results never complete the expensive licensing process for human use – can be co-opted for use in populations of highly endangered species such as gorillas and chimpanzees.

The study was supported by an unusual constellation of organizations, including the Universities of Cambridge and Louisiana, the conservation charity Apes Incorporated, the US Army Medical Research Institute of Infectious Diseases and the biotech company Integrated BioTherapeutics Inc.  The work was conducted at the US’s New Iberia Research Center in Louisiana, one of the research facilities that houses chimpanzees who are not owned by the National Institutes of Health.

This is the first time that a conservation-specific vaccine trial has been undertaken on captive chimpanzees, and proves that a vaccine against Ebola virus is both safe and capable of producing a robust immune response in chimpanzees.

The research team, led by Dr Peter Walsh of the University of Cambridge, administered captive chimpanzees with a new virus-like particle (VLP) vaccine being developed by the biotech company Integrated Biotherapeutics for use on humans. While they did not challenge the vaccinated animals directly with Ebola, researchers tested whether antibodies harvested from the chimpanzees’ blood could protect mice against the deadly virus. They also monitored the chimpanzees in case the vaccine produced health complications.

Results showed that the vaccine is safe in chimpanzees. The vaccinated chimpanzees developed robust immune responses, with virus-specific antibodies detected as early as 2 to 4 weeks after the first vaccination in some animals and within 2 weeks of the second vaccination in all animals.

The antibody transfer study is not the only evidence that this vaccine will work. In 2007 a key paper (2) published in The Journal of Infectious Diseases by Dr Kelly Warfield of the US Army Medical Research Institute of Infectious Diseases – who was also first author on today’s PNAS paper – demonstrated that the VLP vaccine used to vaccinate chimpanzees provides rhesus macaques with very robust protection against the Ebola virus. The 2007 paper also highlights earlier studies in mice and guinea pigs that allowed the refining and evaluation of VLP vaccines against challenge with filoviruses such as Ebola and Marburg, work that underpinned the development of this vaccine.

Next steps:  Testing in captive apes prior to field trials

The authors of today’s paper note that these VLP vaccines currently require multiple administrations to reach “full potency”, but could prove the difference between survival and extinction for species that are highly endangered or immunologically fragile but also easy to vaccinate.

Peter Walsh stressed the need to test this vaccine on captive ape populations prior to field trials.

We need to be pragmatic about saving these animals now before they are wiped out forever, and vaccination could be a turning point. But park managers are adamant – and rightly so at this stage – that all vaccines are tested on captive apes before deployment in the wild. This means access to captive chimpanzees for vaccine trials.”

The ability to test new vaccines for conservation purposes relies on research access to captive chimpanzees, but this access is now under threat just as the recognition of its necessity is increasing in the conservation community.

The US Fish and Wildlife Service is now considering regulations that would end all biomedical testing on captive chimpanzees over the next few years – the US being the only developed country to allow such research. The study’s authors believe that the US should establish a “humanely housed” captive chimpanzee population dedicated solely to conservation research.  The US already has research facilities with humane housing, including social groups, complex enclosures, expert behavioral management to provide enrichment, cognitive engagement, excellent clinical care and chimpanzees trained for cooperative clinical procedures. Thus, it is possible that the need for conservation research could be met by existing populations or centers.

Peter Walsh suggests that, by ending captive research in an effort to pay back an “ethical debt” to captive chimpanzees, the US Government is poised to “renege on an even larger debt to wild chimpanzees” at risk from viruses transmitted by tourists and researchers – as safety testing on captive chimpanzees is required before vaccines can be used in the wild.

“There is a large pool of experimental vaccines that show excellent safety and immunity profiles in primate trails but are never licensed for human use, we’ve demonstrated that it’s feasible for very modestly funded ape conservationists to adapt these orphan vaccines into conservation tools, but the ability to trial vaccines on captive chimps is vital. Ours is the first conservation-related vaccine trial on captive chimpanzees – and it may be the last.

“Although Congress specifically instructed the National Institutes of Health (NIH) to consider the conservation value of captive chimpanzee research, no findings on its possible impact were presented (in the 2011 Institute of Medicine report – SR). If the biomedical laboratories that have the facilities and inclination to conduct controlled vaccine trials ‘liquidate’ (by which he means retire to sanctuaries – SR) their chimpanzee populations, there will be nowhere left to do conservation-related trials.”

Consideration of the work, its continuation, and implications for wild chimpanzees poses challenging ethical questions, particularly in light of recent changes in US chimpanzee research.  They are questions worth serious discussion not only to inform the future of the vaccine research and conservation efforts, but also because they highlight some of the core issues in decision-making about nonhuman animal research.  Primary among the philosophical and pragmatic questions is whether it is ethical to subordinate the interests of individual animals to those of the species, or of other species.  Should some captive chimpanzees be subjected to invasive, infectious disease research in order to potentially benefit wild apes—not only chimpanzees, but also the gorillas who are most threatened by Ebola?  Another set of questions surround which chimpanzees should be used in this research.  Should it be chimpanzees housed in research facilities in the US who are now to be retired to sanctuaries?  Chimpanzees privately owned by research facilities in the US?  Zoo chimpanzees in Europe who are not intended to breed?

While none of these questions are new, progress in Ebola vaccine development and testing puts into sharp relief the kinds of serious ethical challenges that should engage both the scientific community and the broad public.  The questions are not, as the quote from Peter Walsh suggests, relevant only in the US, they are—like many issues in conservation—global.  The results of scientific study and medical progress are not limited to the country in which the research is performed and in this case, it is the global community that has interests in protecting highly endangered African ape populations.

Ethical consideration of conservation goals vs individual ape’s interests

Invasive research with chimpanzees is permitted in a number of countries, including both the US and the UK, when the goal of the research is to benefit the species itself.  At the heart of this justification is priority of the interests of the species, rather than the interests of the individual animal. Subordinating the individual ape’s interests to those of his own species is generally consistent with conservation and environmental ethics, where the basic overarching goal is protection of natural resources, balance, and preservation of endangered species.

By contrast, the basic position of those arguing for personhood for great apes, or for animal rights, is to protect the interests of the individual. From the latter perspective, using captive chimpanzees to develop and test a vaccine for a disease that they do not have and that is unlikely to pose a threat to them, would be ethically prohibited.

It is the conservationist position that appears compatible with performing infectious disease and invasive research with captive animals in order to potentially protect highly endangered wild populations from a disease that greatly affects their survival and future.  Whether the species’ interests should outweigh the individual’s as ethical justification for the research and testing is not the only question, however.  We might also ask which individuals should serve in the research?  Should these be laboratory chimpanzees?  Those living in zoos?  Sanctuaries?  The research was conducted in the US, but just as well could be conducted in the UK or other countries with appropriate scientific resources and expertise.

The use of chimpanzees in US biomedical research has received a great deal of attention in the past several years, with the frequent assertion that it is one of only two countries that continue chimpanzee research.  What is actually true is that the US has maintained chimpanzees in research facilities that serve the global scientific community. Foreign scientists, including the British researcher involved in the Ebola vaccine study and Canadian scientists, conduct research in US research centers with chimpanzees.  Following the recent National Institutes of Health decision to move away from the small amount of invasive and infectious disease research involving chimpanzees and retire almost all of its research chimpanzees, it is now far less clear that the US differs substantially from other countries with respect to being the location where Ebola vaccine research should occur.

Given the nature of the justification for the work, there appears to be no legal reason that it would be opposed in the UK or other countries that allow for invasive studies meant to benefit the species. The real threat is that if chimpanzees are not available in research facilities it will be impossible to test vaccines to protect wild apes against deadly diseases, even where regulations permit such research.

So the primary obstacle to performing this work in the UK or elsewhere in the EU might be the absence of laboratory chimpanzees; however, like many countries, the UK does hold captive chimpanzees in other types of facilities. The justification for the work appears to fall within current use of European zoo chimpanzees for research to improve the health of the individual or the species, a recent example being research on heart disease in Zoo ape populations. In addition while the EU Directive on animals in scientific research forbids the use of apes in biomedical research, this ban does not cover “veterinary clinical trials required for the marketing authorisation of a veterinary medicinal product” which would cover vaccines against Ebola or other infectious diseases.

The inherent weighting of species’ interests over the individual’s interests for the Ebola vaccine work is  consistent with the ethical justification often offered for keeping endangered species captive in zoological parks in order to serve conservation goals.  These goals are thought to be served in two ways in zoos: First, by allowing animals to reproduce in carefully managed breeding schemes where decision-making is driven by the goal of maintaining genetic diversity.  In this way, populations of endangered animals are continued within protected environments to guard against the species becoming extinct should the wild population disappear.  The interests of the individual animals may be served by the management practices, but the individual’s welfare is not the primary consideration. Thus, individuals may be removed from stable social groups to move to other zoos and form new breeding pairs, other individuals may not have the opportunity to reproduce.  Surplus males may be castrated, or may live in all-male social groups.  The recent controversy over the killing of a young male giraffe in a Danish zoo provided a vivid example of subordinating an individual animal’s interests to those of the group, species, or zoo.

A second justification offered for zoos is that they provide opportunities for public education that in turn can increase public support for conservation in the wild. The first goal could be served by keeping animals in situations without public display, in sanctuary or private park settings. Thus, it is this second goal that is the primary justification for public zoos. Given that the primary ethical justification for maintaining captive apes in zoos is related to conservation, the idea of considering these animals within the pool of eligible research subjects for vaccine development and testing to serve conservation goals is not unreasonable.

Consideration of the work by Peter Walsh, Kelly Warfield and colleagues, its next steps, and implications for wild chimpanzees poses challenging ethical questions.  The choice to develop and test a vaccine may harm individual animals, but benefit some of their species and other apes, in this case gorillas (and potentially also humans if the threat from Ebola grows). Some will argue that it is wrong to use individual animals in work that does not benefit them directly, though benefit to others has long been considered an adequate justification for clinical trials in humans. Here, ruling out benefits to others as a justification for research would eliminate the possibility of a vaccine that could save highly endangered wild populations.

Questions about which animals serve in research and where the work is undertaken clearly merit serious consideration that takes into account global responsibilities and the recent changes in US chimpanzee research.  Today’s announcement demonstrates that making choices about animal research is complex, with harms not only in action, but also inaction.  The work should stimulate serious, thoughtful discussion not only within the scientific, conservation, and animal protection communities, but also among policy makers and the wider public.

Paul Browne, PhD and Allyson J. Bennett, PhD

1. Warfield KL, Goetzmann JE, Biggins JE, Kasda MB, Unfer RC, Vu H, Aman MJ, Olinger GG, Walsh PD “Vaccinating captive chimpanzees to save wild chimpanzees” PNAS 2014 Published online 26 May 2014. http://www.pnas.org/cgi/content/short/1316902111
2. Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S. “Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge.” J Infect Dis. 2007 Nov 15;196 Suppl 2:S430-7. PMID: 17940980

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