In the research to combat Covid-19, one of the most important, and in demand, animals to use as models for understanding the virus, and for assessing potential drugs and vaccines, are monkeys. Dan Simonsen takes a look at some of this research.
Having such a close genetic relationship to humans, monkeys are one of the most controversial animal models used in research. Less than one per cent of the animals used in research in the EU are monkeys, however their value in providing the most reliable information for what is happening, or what is going to happen, in humans cannot be underestimated.
It is also the case that under European Directive 2010/63 monkeys are only used when it is not possible to use a non-animal model, or even another species of animal for the research being undertaken.
It follows that researchers around the globe are making use of monkeys to battle Covid-19, including identifying better monkey models, testing the leading vaccine and drug candidates such as remdesivir, and understanding key features of the virus’s biology.
Based on the information on the interactive map, that EARA has produced, on the use of animals in Covid-19 research there have been at least 30 studies that have used monkeys.
Here we look at just some of the studies, either basic research or for drug development, currently being conducted using monkeys in the search for treatments for coronavirus.
Developing an animal model
Research into the suitability of different monkey species to serve as a model has shown that macaques, a type of monkey, are so far the best choice. This basic research is at the heart of gaining a proper understanding of how the disease is transmitted, how it develops and the effect it has on the body.
A recent study from a collaboration of Dutch and German institutions, including EARA member the Biomedical Primate Research Centre (BPRC), in the Netherlands, has demonstrated the suitability of cynomolgus macaques as animal models for testing preventative and therapeutic strategies to combat Covid-19. The studies showed that injecting eight macaques with the virus caused disease similar to that seen in humans, including similar age-related effects.
Another study from China demonstrated age-related effects in rhesus macaques, the most widely used monkey model, with the virus causing more severe pneumonia in older monkeys along with faster replication of the virus, parallel to what is observed in humans.
A study conducted by various institutions in China, including the Wuhan Institute of Virology, also found that infection with the virus caused pneumonia in rhesus macaques, a symptom common in severe cases in humans. Both this study and the one at BPRC, identified that these were a good model to study how the disease might develop and progress in the human body.
Here is a list of other institutions, identified by EARA around the globe, which are working on developing monkey models:
Texas Biomedical Research Institute in collaboration with the Southwest National Primate Research Center, USA - Studying Covid-19, testing detection methods, and identifying treatments.
UW–Madison, USA - Understanding how much of the virus infects the body and where, and to test treatments.
UC Davis, USA - For establishing how age influences Covid-19 symptoms and to develop and test treatments.
Inserm, CEA, Université Paris-Saclay, National Infrastructure for Biology and Health (IDMIT), France - Exploring cynomolgus monkeys as an experimental model.
Tulane National Primate Research Center (TNPRC), USA - Studying the clinical progression and transmission of Covid-19.
A particularly important insight gained from studies using monkeys was that infection is unlikely to reoccur. Researchers from Peking Medical College and the Capital Medical University, in China, demonstrated that rhesus macaques could not be reinfected with Covid-19, indicating that the initial exposure to the virus in humans will likely protect from future infection. This work has vital implications for vaccine design in terms of how long they will be effective for.
Testing leading vaccine and drug candidates
Before treatments to either prevent or treat Covid-19 are ready for human trials, it is first important to test it in animal models to determine if they are likely to be effective and most importantly safe. This may be particularly the case with a Covid-19 vaccination as experience with SARS, a similar coronavirus, indicates the potential for immune complications from the vaccination.
“Without an animal model that closely replicates what goes on in humans, there’s potential for harm in a fast-moving pandemic response like the one mobilising now,” said Dr. Jay Rapport, director of the Tulane National Primate Research Center (TNPRC), talking to WIRED magazine.
As monkeys are so similar to humans, once again they are frequently being used for testing these Covid-19 treatments.
“This [monkeys] is going to be our near clinical model that we’re going to rest heavily on,” said Dr. Chad Roy, a monkey researcher at TNPRC.
One of the most promising and highly publicised treatments in development, remdesivir, has recently been tested on rhesus macaques by the National Institutes of Health and Gilead Sciences, USA. The results showed that early treatment in Covid-19 patients is likely to prevent progression of severe pneumonia.
Rhesus macaques have also been used in safety and efficacy testing of Sinovac’s PicOVacc Covid-19 vaccine, the research found that the vaccine produced partial or complete protection against the virus and suggests that it is safe for use in humans.
Similarly, the global leading vaccine candidate, from the University of Oxford, UK, was recently tested on rhesus macaques as well, finding that the vaccinated monkeys had much lower levels of the virus than unvaccinated monkeys.
“The rhesus macaque is pretty much the closest thing we have to humans,” said Dr. Vincent Munster, who led the primate research testing for the Oxford vaccine.
As there are a large number of treatments in development, there is therefore a large demand for coronavirus testing in monkeys, which has spurred research laboratories to offer testing on macaques at an accelerated timescale, for example with VRL now offering results within 48-72 hours.
Many other institutions are conducting similar tests using monkeys, here is a list of a few of them identified from EARA interactive map:
Genexine - Neutralising antibodies confirmed in preclinical vaccine trial.
Imperial College London, UK - Preclinical vaccine testing.
Fort Detrick - Preclinical vaccine testing.
University of Washington School of Medicine, USA - Preclinical trials of a DNA/RNA vaccine.
VIB, Belgium, & German Primate Center - Leibniz institute for primate research, Germany - Antibody therapeutic, neutralising antibodies confirmed in preclinical antibody therapeutic trial.
Inovio Pharmaceuticals - Preclinical trials of a DNA/RNA vaccine.
Beth Israel Deaconess Medical Center, Israel- DNA vaccine protection against Covid-19 in rhesus macaques.
See here for more information on how monkeys are used in other areas of biomedical research.