Researchers compare rhesus and cynomolgus macaques for SARS-CoV-2 vaccine trials

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent that has sparked the current coronavirus disease 2019 (COVID-19) pandemic. The zoonotic virus (i.e., a pathogen of animal origin that has jumped to human hosts) first emerged in Wuhan, China, in late-2019. Since then, SARS-CoV-2 has spread to 190 countries and territories, infected over 50 million people, and has claimed over 1.25 million lives.

To date, there is no available vaccine or treatment for the viral infection. Though scientists are currently awaiting the results of clinical trials, a vaccine is not likely to be widely available for public use until some point next year (2020).

In clinical trials of interventions and vaccines, animal models are often used to aid in the testing process. Two primate species from the same Macaca genus – rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) – are being widely used in biomedical research and have served as models for SARS-CoV-2 infection.

A team of researchers at the Biomedical Primate Research Centre based in the Netherlands have aimed to determine the effects of the SARS-CoV-2 pathogen on these monkeys and, subsequently, whether they make good animal models for future research in the area.

Animal models for research

For years, research has involved the use of animal models. Medical researches, for instance, uses animals to test drugs, treatments, or vaccines.

In the COVID-19 pandemic, animal models have played a pivotal role in testing potential vaccines and drugs. They can help in the development of safe and effective vaccines and medicines against COVID-19.

Animal models are used to investigate the progression of infection and disease development. Also, they help evaluate prophylactic and therapeutic options, which can help provide a better understanding of the SARS-CoV-2 and its effects on the body.

Mice are usually used in medical research since they are found to be susceptible to infection with SARS-CoV-2. Meanwhile, ferrets have been long used to study the pathology and transmission of respiratory viruses, such as influenza viruses.

Though the use of mice and ferrets provide considerable contributions to research on SARS-CoV-2, non-human primates (NHPs) will likely play a more pivotal role in future studies.

“Due to their similarity to humans, specifically, non-human primates can play a pivotal role in this type of preclinical research. To best appreciate the potential of the various macaque species as SARS-CoV-2 infection models, a thorough characterization of the course of infection is needed,” the researchers explained.

The study

The study, which is available on the preprint bioRxiv* server, highlights the course of SARS-CoV-2 infection in the two genetically close-related macaque species.

To arrive at the study’s findings, the researchers inoculated the monkeys with the SARS-CoV-2 pathogen. Then, the team monitored the monkeys’ clinical, virological, and immunological characteristics. They also compared SARS-CoV-2 replication in cynomolgus macaque species and monitored signs of COVID-19 infection for three weeks after infection.

In the study, the monkeys were infected with the same virus and received the same treatment. They also underwent the same diagnostic examinations, which aimed to monitor lung disease. These include computed tomography (CT) scan of the lungs and continuous telemetric recording of body temperature and activity.

To measure the body temperature and activity, each animal was continuously monitored using a Physiotel Digital telemetric device.

The study results

The researchers found that both species exhibited slightly elevated body temperatures in the first few days after their exposure to the virus. In terms of behavior, the researchers noted that the rhesus macaques manifested decreased physical activity.

Further, the team detected the virus in tracheal, nasal, and anal swabs, including in blood samples from real-time quantitative polymerase chain reaction (qRT-PCR) tests. Both animal species showed similar results.

On the tenth day after infection, both monkeys had immunoglobulins, which were detected by enzyme-linked immunosorbent assays (ELISAs). The results showed seroconversion in all animals.

Lastly, the cytokine responses were observed in both species, while their CT scans showed pulmonary lesions.

“We conclude that the course of SARS-CoV-2 infection of both macaque species is highly similar, indicating that they are equally suitable models to test vaccines and antivirals in a preclinical setting for safety and efficacy,” the team concluded in the study.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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