ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.
ABSTRACT
Omicron (B.1.1.529) is the most recent SARS-CoV-2 variant of concern (VOC), which emerged in late 2021 and rapidly achieved global predominance in early 2022. In this study, we compared the infection dynamics, tissue tropism and pathogenesis and pathogenicity of SARS-CoV-2 D614G (B.1), Delta (B.1.617.2) and Omicron BA.1.1 sublineage (B.1.1.529) variants in a highly susceptible feline model of infection. While D614G- and Delta-inoculated cats became lethargic, and showed increased body temperatures between days 1 and 3 post-infection (pi), Omicron-inoculated cats remained subclinical and, similar to control animals, gained weight throughout the 14-day experimental period. Intranasal inoculation of cats with D614G- and the Delta variants resulted in high infectious virus shedding in nasal secretions (up to 6.3 log10 TCID50.ml-1), whereas strikingly lower level of viruses shedding (<3.1 log10 TCID50.ml-1) was observed in Omicron-inoculated animals. In addition, tissue distribution of the Omicron variant was markedly reduced in comparison to the D614G and Delta variants, as evidenced by in situ viral RNA detection, in situ immunofluorescence, and quantification of viral loads in tissues on days 3, 5, and 14 pi. Nasal turbinate, trachea, and lung were the main - but not the only - sites of replication for all three viral variants. However, only scarce virus staining and lower viral titers suggest lower levels of viral replication in tissues from Omicron-infected animals. Notably, while D614G- and Delta-inoculated cats had severe pneumonia, histologic examination of the lungs from Omicron-infected cats revealed mild to modest inflammation. Together, these results demonstrate that the Omicron variant BA.1.1 is less pathogenic than D614G and Delta variants in a highly susceptible feline model. Author SummaryThe SARS-CoV-2 Omicron (B.1.1.529) variant of concern (VOC) emerged in South Africa late in 2021 and rapidly spread across the world causing a significant increase in the number of infections. Importantly, this variant was also associated with an increased risk of reinfections. However, the number of hospitalizations and deaths due to COVID-19 did not follow the same trends. These early observations, suggested effective protection conferred by immunizations and/or overall lower virulence of the highly mutated variant virus. In this study we present novel evidence demonstrating that the Omicron BA.1.1 variant of concern (VOC) presents a lower pathogenicity when compared to D614G- or Delta variants in cats. Clinical, virological and pathological evaluations revealed lower disease severity, viral replication and lung pathology in Omicron-infected cats when compared to D614G and Delta variant inoculated animals, confirming that Omicron BA.1.1 is less pathogenic in a highly susceptible feline model of infection.
