Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

Abstract

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and dysregulation at later time points that can also be identified in humans

“…Released virus then goes on to infect new epithelial cells with virus infection increasing exponentially in waves but becoming asynchronous. The decline in sgmRNA from Day 8/9 overlaps with IgG seroconversion and humoral immunity in both species 18 and follows similar kinetics to serology profiles measured in patients with COVID-19.…”

“…This tends to be 5 to 6 days post-exposure. In the absence of a human challenge model, animal models can be used to study the kinetics of SARS-CoV-2 18, 19 . Two separate non-human primate models, cynomolgus and rhesus macaques, were established for the study of SARS-CoV-2 that mirrored disease in the majority of humans 18 .…”

“…In the absence of a human challenge model, animal models can be used to study the kinetics of SARS-CoV-2 18, 19 . Two separate non-human primate models, cynomolgus and rhesus macaques, were established for the study of SARS-CoV-2 that mirrored disease in the majority of humans 18 . To study the pattern of sgmRNA synthesis over the course of infection, nasopharyngeal samples were sequentially gathered daily from one day post-infection up to 18 days post-infection from the two NHP models.…”

“…In the absence of a human challenge model, NHP models that closely resemble COVID-19 disease in humans can be used to study SARS-CoV-2 infection, from a very defined initial exposure. RNA was sequenced from longitudinal nasopharyngeal samples from two NHP models, rhesus and cynomolgus macaques 18 . LeTRS used to identify the abundance of the leader-TRS gene junctions in this data.…”

A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

“…This was primarily due to macaque availability at the time the study was conducted. However, this appears to have been both a strength [64] and weakness of the experimental design, as we found similar lung pathology in the cynomolgus macaque as well as similar patterns of BAL gene expression as the controls Rhesus subjects [72], and 5) we did not study the effects of adjuvant alone on SARS-Cov-2 infection in the Rhesus macaques. Previous experience with this microsphere CTL vaccine platform in a murine Ebola virus model has shown that adjuvant alone was not sufficient to confer protection against lethal virus challenge.…”