Developing a crucial animal model for studying COVID-19

2020

Challenge

In the face of a global pandemic, moving experimental treatments and vaccines from the bench to the bedside is of the utmost importance. A non-human primate model that closely resembles the moderate COVID-19 disease that has been observed in the majority of human cases would allow scientists to conduct critical studies of the illness and the virus that causes it, known as SARS-CoV-2, as well as the effects of therapeutics and vaccines.

Advance

IRP investigators at NIH’s Rocky Mountain Laboratories facility in Montana quickly established the first widely used non-human primate model of COVID-19 and used it to perform the critically needed preclinical testing of the AstraZeneca vaccine, the antiviral drug remdesivir, and other potential treatments for COVID-19. Using this model, they showed that animals that received remdesivir during the early stages of infection displayed significantly better health than those that were not treated. In addition, they showed that AstraZeneca’s vaccine significantly reduced the amount of virus in the lungs of animals exposed to SARS-CoV-2 compared to unvaccinated animals. Vaccination also prevented the development of pneumonia in animals exposed to the virus.

Impact

The animal studies performed at Rocky Mountain Laboratories allowed critical assessment of the safety, immune response, and efficacy profiles of remdesivir and the AstraZeneca vaccine against COVID-19, which was necessary before they could be tested in human clinical trials. As such, the studies were an essential step toward the use of these lifesaving measures in humans. The IRP researchers’ model has since been adopted by many other institutions and is being utilized for the preclinical development of the IRP’s future vaccine candidates.

Publications

Munster VJ, Feldmann F, Williamson BN, van Doremalen N, Pérez-Pérez L, Schulz J, Meade-White K, Okumura A, Callison J, Brumbaugh B, Avanzato VA, Rosenke R, Hanley PW, Saturday G, Scott D, Fischer ER, de Wit E. (2020). Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature. Sep;585(7824):268-272. doi: 10.1038/s41586-020-2324-7.

Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, van Doremalen N, Leighton I, Yinda CK, Pérez-Pérez L, Okumura A, Lovaglio J, Hanley PW, Saturday G, Bosio CM, Anzick S, Barbian K, Cihlar T, Martens C, Scott DP, Munster VJ, de Wit E. (2020). Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. Sep;585(7824):273-276. doi: 10.1038/s41586-020-2423-5.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, Avanzato VA, Bushmaker T, Flaxman A, Ulaszewska M, Feldmann F, Allen ER, Sharpe H, Schulz J, Holbrook M, Okumura A, Meade-White K, Pérez-Pérez L, Edwards NJ, Wright D, Bissett C, Gilbride C, Williamson BN, Rosenke R, Long D, Ishwarbhai A, Kailath R, Rose L, Morris S, Powers C, Lovaglio J, Hanley PW, Scott D, Saturday G, de Wit E, Gilbert SC, Munster VJ. (2020). ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. Oct;586(7830):578-582. doi: 10.1038/s41586-020-2608-y.