Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell-and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.

12Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global 13 pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to 14 screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model 15 for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green 16 monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may 17 be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In 18 addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late 19 as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be 20 produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been 21 employed in other NHP studies. 42varying degrees of non-lethal illness when the virus was delivered into the respiratory tract of these animals [7-43 13]. While each of these models has utility in the study of COVID-19, NHPs have the closest physiological 44 resemblance to humans allowing a better comparison of host responses to infection. This genetic similarity has 45 also contributed to the increased availability of reagents to perform in-depth analyses of the immune response. 46Recently, the first studies evaluating the pathogenic potential of SARS-CoV-2 in cynomolgus and rhesus 47 macaques were performed. Rhesus macaques developed pneumonia and clinical signs whereas disease in 48 cynomolgus macaques was fairly mild indicating the former appears to better reflect more severe cases of 49 . These results suggest certain NHP species may serve as better models than others for 50 4 coronavirus infections. For SARS, the disease caused by SARS-CoV-1, African green monkeys (AGMs) were 51 found to support the highest level of viral replication, followed by cynomolgus macaques and rhesus macaques 52 when all three species were challenged in parallel [14]. Only AGMs had notable replication in the lower 53 respiratory tract following SARS-CoV-1 inoculation; necropsy of these animals indicated focal interstitial 54 mononuclear inflammatory infiltrates and edema in the lung consistent with human SARS. As SARS-CoV-1 and 55 SARS-CoV-2 share the same putative host receptor angiotensin-converting enzyme 2 (ACE2) [15, 16], we 56 reasoned that AGMs might serve as a useful model for COVID-19. 57Here, we infected AGMs with a low passage isolate of SARS-CoV-2 (SARS-CoV-2/INMI1- 58Isolate/2020/Italy) and evaluated their potential as a model for COVID-19. SARS-CoV-2/INMI1-Isolate/2020/Italy 59 was isolated from the first clinical case in Italy [17] and is the first V clade virus (GISAID) to be experimentally 60 inoculated into NHPs. We demonstrate AGMs mimic several aspects of human disease including a high degree 61 of viral replication and severe pulmonary lesions. T...

The recent outbreaks of Zika virus (ZIKV) infection in French Polynesia, the Caribbean, and the Americas have highlighted the severe neuropathological sequelae that such an infection may cause. The development of a safe, effective ZIKV vaccine is critical for several reasons: (i) the difficulty in diagnosing an active infection due to common nonspecific symptoms, (ii) the lack of a specific antiviral therapy, and (iii) the potentially devastating pathological effects of in utero infection. Moreover, a vaccine with an excellent safety profile, such as a nonreplicating, noninfectious vaccine, would be ideal for high-risk people (e.g., pregnant women, immunocompromised patients, and elderly individuals). This report describes the development of a recombinant subunit protein vaccine candidate derived from stably transformed insect cells expressing the ZIKV envelope protein in vitro, the primary antigen to which effective virus-neutralizing antibodies are engendered by immunized animals for several other flaviviruses; the vaccine candidate elicits effective virus-neutralizing antibodies against ZIKV and provides protection against ZIKV infection in mice.

Zika Virus (ZIKV), a virus with no severe clinical symptoms or sequelae previously associated with human infection, became a public health threat following an epidemic in French Polynesia 2013–2014 that resulted in neurological complications associated with infection. Although no treatment currently exists, several vaccines using different platforms are in clinical development. These include nucleic acid vaccines based on the prM-E protein from the virus and purified formalin-inactivated ZIKV vaccines (ZPIV) which are in Phase 1/2 clinical trials. Using a recombinant subunit platform consisting of antigens produced in Drosophila melanogaster S2 cells, we have previously shown seroconversion and protection against viremia in an immunocompetent mouse model. Here we demonstrate the efficacy of our recombinant subunits in a non-human primate (NHP) viremia model. High neutralizing antibody titers were seen in all protected macaques and passive transfer demonstrated that plasma from these NHPs was sufficient to protect against viremia in mice subsequently infected with ZIKV. Taken together our data demonstrate the immunogenicity and protective efficacy of the recombinant subunit vaccine candidate in NHPs as well as highlight the importance of neutralizing antibodies in protection against ZIKV infection and their potential implication as a correlate of protection.

No abstract