In December 2019, a respiratory disease caused by a previously unknown coronavirus, SARS-CoV-2, was reported for the first time. The centre of the outbreak was Wuhan, China. Since then, the virus has spread rapidly across the world and not long after that, the World Health Organization (WHO) declared the outbreak a pandemic in March 2020.
SARS-CoV-2 causes an acute respiratory illness we now know as Coronavirus Disease 2019 (COVID-19), which is characterized by a wide range of symptoms including fever, dry cough, fatigue and loss of smell or taste. The severity of COVID-19 soon proved to be associated with age and/or underlying illnesses such as high blood pressure and obesity, and may lead to hospitalization (in intensive care unit) and eventually death. However, seemingly healthy young people can be severely affected by the virus as well. It is very worrying that a large group of people – including those who only had mild symptoms after first falling ill – developed various severe complications for a very long time after the initial infection. This clinical picture is called long Covid. So far, SARS-CoV-2 has infected 650 million people and killed 6.6 million worldwide (21 December 2022, https://covid19.who.int).
Possibility of testing vaccines in monkeys
Both the scientific and the medical worlds have played a major role in the fight against coronavirus. Shortly after isolating and characterising the virus, the development of vaccines against this virus began. Several pharmaceutical companies already had a few vaccines "at the ready" that only needed to be adjusted slightly to work against SARS-CoV-2. Though, a suitable animal model was vital to test the efficacy of these vaccines. Studies with known coronaviruses have shown that monkeys are susceptible to coronavirus infection. At the beginning of 2020, BPRC conducted together with Erasmus MC one of the first experimental infection studies in monkeys in Rotterdam. Because of this study, we know for certain that monkeys can contract the virus and that the infection causes mild COVID-19 symptoms.
On 17 March 2020, BPRC was granted permission by the Central Authority for Scientific Procedures on Animals to use monkeys for COVID-19 research. This paved the way to develop in-house models that could be used to test vaccine candidates at a later stage. The first experimental infection at BPRC, in mid-April 2020, kept both the animal care workers and veterinarians as well as the researchers in suspense. The infection and accompanying symptoms in monkeys were examined in detail and no unexpected manifestations were observed. Because of CT scans, among other things, we now know that SARS-CoV-2 infection in monkeys is comparable to a mild infection in humans. You can read a summary of the first year of our COVID-19 research here: One year of COVID-19 research at BPRC; we look back.
Virus mutations
Shortly after publishing our findings, many requests came in from the scientific and medical worlds to test several vaccine candidates in our monkeys for safety and efficacy. SARS-CoV-2 could, however, mutate/change quickly, which meant we had to adjust our infection models regularly to the most prominent virus variant at that time. This change is usually so small that it hardly affects the clinical picture but sometimes it causes a virus, for example, to act differently and spread more easily. To understand this process, we have regularly infected a few animals with SARS-CoV-2 variants circulating at that time to see whether the infection would manifest itself more severely or last longer. Over the last 3 years, we have conducted infection studies with several SARS-CoV-2 variants: 2 Betas, a Delta, and finally an Omicron.
Vaccine candidates
Monkeys have been vaccinated with several vaccine candidates since May 2020. During the past 3 years, BPRC has carried out 9 large vaccine studies – usually with several experimental vaccines in each study – and a protocol to test a therapeutical monoclonal antibody against SARS-CoV-2 for efficacy against infection or disease progression. One of the vaccine candidates BPRC has contributed to has been administered to people via a global vaccination campaign for 18 months now. Three other candidates are part of clinical trials to evaluate them further on safety and efficacy. The monoclonal antibody is being tested in a clinical trial as well and we know that clinical trials for two more vaccine candidates are going to start soon.
Besides testing a vaccine, we can also study the effects of SARS-CoV-2 infection on various organs, such as the lungs and the brain, which may help us find the underlying mechanisms of long Covid.
Publications
One of the conditions to do research in collaboration with BPRC is that the results will be published in academic literature. We were able to publish many of the studies mentioned above, often in top-ranked scientific journals. This is an overview of our publications: Rockx et al., Science 2020; Brouwer et al., Science 2020; Genzel et al., Curr Biol 2020; Sanchez-Felipe et al., Nature 2021; Solforosi et al., J Exp Med 2021; Maaskant et al., Plos One 2021; Marchi et al, Plos One 2021; Böszörményi et al., Viruses 2021; Embregts et al., One Health 2021; Mooij et al., Front Immunol 2022; Volkmann et al., Front Immunol 2022; Trombetta et al., Hum Vacc Immunother 2022; Philippens et al., Viruses 2022; Meijer et al., Nucl Med Biol 2022; Grobben et al., Microbiol Spect 2022; Clarreaux et al., Nat Comm 2022. In addition, several other papers are currently being peer-reviewed or prepared for publication.
Visible
Despite the heavy workload and mental strain for all employees, these important results could be achieved by working in close collaboration. It is exactly what BPRC excels in. Our preclinical research programme anticipates current health issues arising from science and society. The COVID-19 pandemic suddenly made our work very visible, not only through scientific publications but also via several news media. In recent years, the following national press reached out to us: NU bij BPRC, Algemeen Dagblad bezocht BPRC, Dagblad Trouw op bezoek, BPRC op radio 1, De Volkskrant volgde twee apen van BPRC in een COVID-studie, Volkskrant journalist Maartje Bakker wint internationale prijs met verhaal over Chips en Dip, BPRC onderzoeker te gast bij online praatprogramma.
Anticipating quickly
Since the start of the COVID-19 pandemic, BPRC has been at the forefront of vaccine development. That is exactly the purpose of this institute: conducting scientific research on life-threatening and serious diseases, and using that knowledge to find remedies for these kinds of diseases. During this pandemic, we have certainly shown that – reacting effectively if the demand is urgent. Our unique, well-characterized monkey breeding colony allows us to anticipate rapidly. The research continues: there will probably be second-generation COVID-19 vaccines, long Covid requires a great deal of attention and there still are a lot of infectious diseases causing a great deal of harm.
A word of thanks
Everything we have accomplished during these past few years wouldn't have been possible without the help of various external and internal authorities: such as the bodies that were responsible for obtaining ethical approval (CCD, DEC), VAC that has created several safety protocols allowing employees to carry out the studies in a safe way and finally, IvD that has assessed various project applications, often with tight deadlines and even more often on an ad hoc basis. We also express our appreciation for the hard work done by the employees of BPRC, people who often had to work against the clock and sometimes in demanding conditions during various working hours. The process was and still is a team effort of all departments. And of course, we won't forget that our monkeys have played a crucial role and proved to be invaluable in the fight against serious diseases such as, in this case, COVID-19.