The importance of nonhuman primates during the SARS-CoV-2 pandemic

Animal models have always played a pivotal role in scientific research for understanding disease mechanisms, drug discovery, and the development of vaccines and therapeutics. This thesis focuses on the importance of nonhuman primates (NHPs) in infectious disease research, particularly during the COVID-19 pandemic. Due to their physiological and genetic similarities to humans, NHPs were crucial in studying SARS-CoV-2 pathogenesis and developing vaccines. The thesis describes the experimental infection of rhesus and cynomolgus macaques with SARS-CoV-2 to establish a model for vaccine evaluation. Analyses revealed prolonged lung pathology, widespread tissue dissemination, and the neuroinvasive potential of the virus, with viral RNA detectable in several brain regions weeks after infection. Gastrointestinal involvement was also observed, accompanied by the shedding of replication-competent virus, indicating the possibility of faecal-oral transmission. Furthermore, our research demonstrated the efficacy of the TSPO tracer, [18F]DPA-714, in visualising inflammatory processes in the lungs of SARS-CoV-2-infected macaques. The thesis also underscores the significant contribution of NHPs to the rapid development of vaccines against COVID-19, including the successful evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine expressing the full-length SARS-CoV-2 S protein. These findings highlight the important role of animal models, particularly NHPs, in scientific research and in fighting a worldwide outbreak.