For several infectious diseases, non-human primates provide an animal model in which the course of disease and induction of pathology resemble that in man.
Dr Jan A M Langermans, of the Biomedical Primate Research Centre, turns the spotlight onto non-human primates and their important role in vaccine development…
Dr Jan A M Langermans
Vaccination is the most reliable and cost-effective means of preventing infectious diseases. Vaccine development started in the 18th
Century with the discovery of the cowpox-based vaccine to prevent smallpox. This first vaccine was still used until recently and has resulted in the eradication of smallpox. Identification of many more of the microorganisms responsible for infectious diseases from the 19th
Century onwards, such as tuberculosis, cholera or typhoid fever, have led to the development of many attenuated or inactivated bacterial and viral vaccines. This has saved many lives.
However, various vaccines developed in this way, especially the older ones, may lack the desired effectiveness or reliability. For example, the current vaccine for tuberculosis has variable efficacy, therefore a new one is urgently needed. Other vaccines seem to lose their effect over time due to adaptation of the pathogen, therefore vaccines against certain viral diseases, e.g. influenza, need to be adapted regularly due to these rapid changes. Research focuses on broadly effective vaccines for such diseases. In addition, the emergence or re-emergence of infectious diseases requires the development of new vaccines. New techniques and knowledge will result in new generations of vaccines based on new delivery methods, biotechnology-derived products, formulations and substances, which, in turn, will lead to more effective and/or more specific vaccines.
These new techniques and the use of such vaccines, however, can also raise concerns in society. In the Netherlands, rumours of the potential side-effects of the human papilloma vaccine used to prevent cervical cancer caused a large group of girls to refuse vaccination, resulting in relatively low vaccination coverage. To limit the chance of unwanted side-effects and to prevent social unrest as much as possible, regulatory authorities require the thorough evaluation of these products regarding their efficacy and, very importantly, their safety in animal models before they can be used in humans.
Animal models are important in studying the fundamental properties of diseases. Well-defined animal models are required for the extensive sampling of infectious diseases, and new prophylactic and therapeutic treatments can be studied in such models to provide proof-of-concept before they advance to expensive clinical trials, thus limiting both risk and time.
Factors that influence the worldwide spread of infectious diseases include the emergence of new pathogens, increased travel and rapid development of antibiotic resistance that makes treatment more difficult. Fast identification of pathogens causing a disease and the development of new vaccines and therapies are therefore essential.
A close resemblance
To study the various aspects of (re)emerging infectious diseases and be able to develop effective vaccines, animal models resembling humans as closely as possible are required. In a number of cases, non-human primates are the closest model to use to study new therapies. Due to the complexity of the various aspects of the immune system and the interaction with other processes in the host, the ultimate efficacy and safety testing of these new compounds still require animal models.
So why are non-human primates used in vaccine research? The main reasons are that they have been shown to be naturally susceptible to many of the pathogens found in humans. Furthermore, the immune system and various physiological processes in non-human primates and humans are comparable. Although mice are very useful in studying immunological reactions in response to vaccines, the predictive value regarding modulation of pathogenesis and vaccine efficacy in these animals is often limited.
For several infectious diseases, non-human primates provide an animal model in which the course of disease and induction of pathology resemble that in man. Non-human primates have therefore played an essential role in vaccine development for a very long time, being instrumental in the development of vaccines against serious infectious diseases like polio, yellow fever and hepatitis B. These animals have also aided in the identification of various pathogens responsible for other diseases, such as the causative agent of tuberculosis.
More recently, the use of non-human primates has been used in the fast identification of the pathogen causing SARS. The inoculation of macaque monkeys with a specific virus isolated from patients with SARS induced a comparable disease in these animals. Since then, various therapies and vaccines against the virus, inducing SARS, have been studied in these monkeys.
Developing safe, reliable vaccines
To predict vaccine immunogenicity and efficacy, there is also a need for preclinical and clinical biomarkers. Biomarkers can be used to rapidly identify the potential of the vaccine, thus saving time and costs. In humans, where infections can’t be timed, characterisation of the predictive biomarkers is difficult. The possibility of introducing controlled infections into a non-human primate model that resembles humans as closely as possible, allows more detailed studies into identifying such markers. New techniques, such as transcriptional profiling of immune responses, will result in the identification of correlates of protection and immune profiles that will predict the effectiveness of vaccines, for example, studies in well-defined vaccination protocols followed by a challenge with the relevant pathogen of non-human primates are crucial to validate these markers and/or profiles.
Non-human primates play an important role in host-pathogen interaction studies and the evaluation of new vaccines. Primates are currently used in vaccine research for major infectious diseases, such as HIV, tuberculosis, measles, influenza and malaria, as well as emerging diseases that are a threat to humans, such as West Nile virus, dengue, Rift Valley fever and Ebola. Future infectious disease threats are not yet known, but non-human primate models are and will be key in the development of safe and reliable vaccines.
The use of non-human primates in research comes with the obligation to take optimal care of these highly social and intelligent animals. Although studies into infectious diseases require strict protection measures that might limit their housing possibilities, well-designed social housing facilities are essential. Well-defined enrichment programmes also have to be in place and ideally all animals are trained to cooperate in order to reduce stress as much as possible. Large investment may be required to obtain these conditions, but if we need to use these animals for the benefit of man we are ethically and morally obligated to provide them with the most optimal situation possible.
Dr Jan A M Langermans
Animal Science Department
Biomedical Primate Research Centre
[This article was originally published on 1st
July 2013 as part of Science Omega Review Europe