- Explained -
Welcome to the 2019 annual scientific report from Biomedical Primate Research Centre (BPRC). In this report our scientists inform you about their work with monkeys and their most important scientific findings. As you will see, our work covers many different aspects, collaborations with (inter)national partners and (inter)national funding agencies. Together, this highlights our work as high standard and scientifically relevant.
On January 1st 2019 BPRC housed 1402 monkeys, 940 rhesus macaques (Macaca mulatta), 286 cynomolgus monkeys (long-tailed macaques; Macaca fascicularis) and 176 common marmosets (Callithrix jacchus). On December 31st BPRC housed 1277 animals, 824 rhesus macaques, 261 long-tailed macaques and 192 common marmosets. In 2019 BPRC worked with 154 animals, 116 rhesus macaques and 38 Longtailed macaques. These numbers were reported to the NVWA.
BPRC is committed to health research and alternatives. The development and implementation of the 3Rs, Refinement, Reduction and Replacement are visible throughout BPRC. In this report you will find many examples of how refinement of animal models leads to a reduction of the number of animals we work with.
Why do we still need animals for research?
BPRC focuses on life threatening and/or debilitating diseases that affect millions of people. Diseases without cure or treatment because the complicated disease mechanisms are not yet fully understood. The European Commission concluded that the type of research conducted at BPRC cannot be done without life animals.
Visualizing invisible disease processes
A patient only seeks medical help when he or she is suffering from disease symptoms. At that time the actual disease-process is already ongoing and caused damage to cells and/or organs. As a consequence, early and asymptomatic stages of a disease cannot be studied in people. To ‘visualize invisible’ disease processes we depend on experimental animal models.
The X-axis represents the time and y-axis disease severity. A disease does typically not start with clinical symptoms. The onset is often without signs. But as time progresses the damage to cells and organs accumulate and cause clinically relevant disease. Depending on the disease this can take days to years. At that point patients go to a doctor and laboratory tests are needed to make a diagnosis. Only when diagnosis is made, proper treatment can start. Most diseases have a so-called point of no return. Before that the damage can be repaired, but when damage progresses beyond that point it results in irreversible (unrepairable) damage. In best case, the disease is diagnosed before the point of no return. Damage caused by the disease is reversible and treatment cures the disease. In case of a chronic disease, the disease cannot be cured. Drugs can help to suppress further disease progression but the damage is irreversible and drugs cannot undo the damage (MS). During a chronic progressive disease, the symptoms are also irreversible and get worse. So far there are no drugs available to stop progression. Some infectious diseases are preventable by a vaccine (measles) or prophylactic drugs (malaria). Studying a disease and potential new medicines in people is only possible after the diagnosis of the disease. To study early events, we rely on animal models that resemble the infection or disease in humans. Understanding early events of a disease enables the identifying of the point of no return, hence decrease overall medical health care costs and increase quality of life. But also, to develop animal-free alternative methods to evaluate new potential medicines.
Creating conditions for animal free alternatives
Unraveling disease processes is not only necessary to identify potential treatments but also to create the conditions for animal free-alternative methods to test vaccines or new treatments. Before one can even think about the development of an animal-free method to evaluate potential drugs or treatment, one needs full understanding of a disease and its critical events.
In a prophylactic vaccine study, a vaccine is used to generate a pathogen-specific immune response. The interplay between thousands of different molecules, including antibodies, cytokines, specific subsets of cells in the blood and chemokines, determine the quality and quantity of the immune response, and thus the protective effect of the vaccine. To test this, the animal is exposed the actual pathogen. The protective capacity of the vaccine is defined by the amount of virus, bacteria or parasite that can be detected after exposure. Little or no pathogen means the vaccine was successful.
Identification of (a combination of) molecule(s) that predict the effectiveness of the vaccine on forehand is a powerful refinement of an animal model. In the first place because evaluation of future new vaccine candidates does no longer require exposure to the pathogen itself to determine the effectiveness of a vaccine and therefore the discomfort of the animal is reduced. And second because it is the first step to the development of animal-free alternative techniques to evaluate potential new vaccine candidates.
Vaccine efficacy studies
Vaccines are a safe way to generate immune memory without the potential risk to develop disease-associated complications. Many infectious diseases can be prevented by vaccines, but for many pathogens vaccines are desperately needed. To evaluate the efficacy an experimental vaccine so called exposure studies are required. After vaccination the immune response is challenged by the actual pathogen. This requires a model that is susceptible to vaccination and the pathogen. This makes rodents often not the best model.
As most vaccines evaluated at BPRC are developed for human use, people would be the best model. However, only for a limited number of infectious diseases human challenge studies are permitted, like malaria and influenza. To limit medical risk for the human volunteers, these human exposure studies are typically performed with weak, attenuated or curable strains of the pathogens, and only with vaccine candidates that have proven safety in animal models. Yet for the vast majority of the vaccine efficacy studies conducted at BPRC human challenge models are not available.
In this report we proudly present our contribution to science, the 3Rs and the development of animal-free alternatives.
More information regarding animals in experiments is found at Stichting Informatie Dierproeven, European regulatory bodies (Directive 2010/63/EU), the Dutch law (Wet op de dierproeven). The Centrale Commissie Dierproeven (CCD) is the legal body in The Netherlands that is authorized to provide licenses. BPRC’s accreditation by AAALAC International guarantees good institutional policies, animal husbandry and welfare, veterinary care at BPRC.