Army scientists evaluated three nonhuman primate species as potential models of SARS-CoV-2 airborne infection, according to results published online this week in PLOS ONE. Their work demonstrates that any of these species may be useful for testing vaccines and therapies in response to the COVID-19 pandemic, which has resulted in over 104 million cases and more than 2 million deaths worldwide in the past year.
Given the global impact of COVID-19, experts are working rapidly to develop medical countermeasures, and testing in animal models is critically important to evaluate the efficacy of these products. Recent studies suggest that aerosol transmission may be the most prevalent route of human exposure to SARS-CoV-2, the virus that causes COVID-19. Until now, however, the African green monkey was the only nonhuman primate model studied in efforts to replicate airborne transmission of the virus.
In this paper, first author Sara C. Johnston, Ph.D., and colleagues at the U.S. Army Medical Research Institute of Infectious Diseases analyzed two additional nonhuman primate species as potential models of COVID-19 in humans.
The team exposed cynomolgus macaques, rhesus macaques, and African green monkeys to SARS-CoV-2 using a model system invented at USAMRIID that generates a controlled dosage of highly respirable airborne particles within a sealed chamber. Scientists then monitored the animals for up to 18 days, documenting clinical disease findings and comparing them to human cases. All three species developed disease that resembled mild acute respiratory disease in human patients, and all had corresponding viral loads in nasal and throat swabs. Respiratory abnormalities and viral shedding also were observed for all animals.
"In general, the clinical disease characteristics we noted are similar to those described by others in the field," Johnston commented. "One exception is the presence of fever in all cynomolgus macaques on this study. This finding was exclusive to cynomolgus macaques and was detected only by using implanted body temperature-monitoring devices. Since fever is a hallmark of COVID-19 for human patients, this represents an important clinical finding."
Developing animal models is a complex process, according to Johnston. Variables include the species selected, the dose of virus used, and the route of exposure, with the goal being to combine these elements to create a model that replicates human disease as closely as possible.
Overall, the USAMRIID data indicate that macaques, in addition to African green monkeys, can be infected by airborne SARS-CoV-2, providing natural transmission models for evaluation of vaccines and treatments.
"In addition to determining critical disease parameters associated with disease progression, and establishing correlations between primate and human COVID-19, this work directly contributes to the advancement of medical countermeasures against the virus," said USAMRIID senior author Aysegul Nalca, M.D., Ph.D. She said the team's next step is to demonstrate the utility of these primate models for the continuing evaluation of vaccine and therapeutic candidates. Having more than one viable model in place, she added, will help to facilitate a more rapid deployment of new medical products to mitigate the COVID-19 pandemic.
About the U.S. Army Medical Research Institute of Infectious Diseases:
For over 50 years, USAMRIID has provided leading edge medical capabilities to deter and defend against current and emerging biological threat agents. The Institute is the only laboratory in the Department of Defense equipped to safely study highly hazardous viruses requiring maximum containment at Biosafety Level 4. Research conducted at USAMRIID leads to medical solutions - vaccines, drugs, diagnostics, information, and training programs - that benefit both military personnel and civilians. Established in 1969, the Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Development Command. For more information, visit http://www.usamriid.army.mil.
"Development of a Coronavirus Disease 2019 nonhuman primate model using airborne exposure" is available at this link:
Sara C. Johnston, Keersten M. Ricks, Alexandra Jay, Jo Lynne Raymond, Franco Rossi, Xiankun Zeng, Jennifer Scruggs, David Dyer, Ondraya Frick, Jeffrey W. Koehler, Paul A. Kuehnert, Tamara L. Clements, Charles J. Shoemaker, Susan R. Coyne, Korey L. Delp, Joshua Moore, Kerry Berrier, Heather Esham, Joshua Shamblin, Willie Sifford, Jimmy Fiallos, Leslie Klosterman, Stephen Stevens, Lauren White, Philip Bowling, Terrence Garcia, Christopher Jensen, Jeanean Ghering, David Nyakiti, Stephanie Bellanca, Brian Kearney, Wendy Giles, Nazira Alli, Fabian Paz, Kristen Akers, Denise Danner, James Barth, Joshua A. Johnson, Matthew Durant, Ruth Kim, Jay W. Hooper, Jeffrey M. Smith, Jeffrey R. Kugelman, Brett F. Beitzel, Kathleen M. Gibson, Margaret LM Pitt, Timothy D. Minogue, and Aysegul Nalca, all of USAMRIID
This research was supported by the Military Infectious Diseases Research Program.